Category: Family

Energy metabolism and autoimmune diseases

Energy metabolism and autoimmune diseases

NovelmiRNA targets the enzyme adenosine disexses deaminase AMPD -2 involved Energy metabolism and autoimmune diseases metabolisj nucleobase or nucleotide metabolism by converting AMP to inosine monophosphate Energh [ Table 1 ; ]. Table 1 Major metabolic pathways in innate cells Full size table. Choi S-CTitov AAAbboud Get al. PLoS One ; e Front Immunol ; Metabolic link between obesity and autoimmune diseases. JCI Insight.

Energy metabolism and autoimmune diseases -

Studies in mice, however, offer clues about how glucose impacts the severity of the disease. For instance, when researchers gave mice with ulcerative colitis glucose-rich drinking water, the mice developed more severe colon inflammation than those that drank plain water.

The glucose-drinking mice also had higher levels of Th17, the cell type that produces inflammatory cytokines. Hyperglycemia-induced damage to the lining of the gut could play a role. A mouse study found that in obese mice, hyperglycemia disrupted the tight junctions between the endothelial cells at the gut-blood barrier, allowing intestinal microbes to escape and spread throughout their bodies.

When the researchers looked for evidence of this same effect in people, they found that those with the highest blood glucose levels had the highest number of immune-stimulating microbial molecules in their blood—a situation that likely promotes colitis.

Early research in people has zeroed in on another potential contributor: adropin , a hormone that helps maintain metabolic homeostasis and may play a rol e in modulating inflammation. People with IBD tend to have lower levels of adropin than usual.

Other researchers have noted low adropin levels in people with rheumatoid arthritis , cardiovascular disease , and insulin resistance. Animal studies add to the picture: In mice, adropin deficiency exasperates glucose dysregulation and insulin resistance ; a study in rhesus macaques found that animals with low adropin levels have increased risk for Type 2 diabetes—and that fructose accelerates their metabolic dysregulation ; and adropin therapy improves insulin resistance and glucose intolerance in obese mice.

Now that researchers have established a link between low adropin levels and IBD, future studies can tease out any causal mechanisms and demonstrate whether a high-glucose diet plays a role. As in rheumatoid arthritis, however, medications confuse the picture.

Glucocorticoids, commonly prescribed when IBD is in a state of a flare-up, nearly triple the risk of Type 2 diabetes in people with IBD according to one extensive analysis—more than in any of the other five autoimmune conditions included in the study. Systemic lupus erythematosus SLE is a progressive autoimmune disease that causes inflammation in connective tissues, including cartilage and the lining of the blood vessels.

It can damage multiple organs and bodily systems, including the joints, skin, heart, kidneys, lungs, and central nervous system, to a degree that ranges from mild to life-threatening.

So much about SLE remains a mystery, but there is an insulin connection: despite having normal glucose tolerance and pancreatic β cell function, people with lupus have raised fasting insulin levels and lowered insulin sensitivity. They are also nearly twice as likely to have metabolic syndrome compared to healthy controls, according to a large meta-analysis that reviewed data from 24 studies.

A small study in children with juvenile SLE found that they, too, are more insulin resistant than healthy controls —regardless of how long they have been sick or how active their disease is.

A meta-analysis found that people with SLE have elevated levels of a trio of hormones: adiponectin, leptin, and resistin. These hormones are secreted by adipose tissue and play essential roles in regulating insulin sensitivity and inflammation. Strikingly, resistin levels appear to increase in step with SLE disease severity.

In another study, SLE disease damage over time seemed to exacerbate the risk of insulin resistance in people with existing risk factors, including high BMI, large waist circumference, and hypertension—suggesting that insulin resistance is a result, rather than a driver, of SLE.

High doses of glucocorticoids are especially problematic in SLE—upping the risk of insulin resistance more than six-fold. A study of primarily females found that people with SLE are 27 percent more likely to have a cardiovascular event ——such as a heart attack or stroke——than those with Type 2 diabetes.

The authors of that study called for further research to identify the underlying factors that put people with lupus at such a high risk of heart disease.

Multiple sclerosis MS is a debilitating autoimmune disease in which the blood-brain barrier becomes compromised, allowing immune cells to invade the central nervous system.

Its core features include widespread inflammation, myelin destruction, neuron loss, and lesions in the brain. There are three types of multiple sclerosis. Relapsing-remitting MS RRMS , secondary progressive MS SPMS , and primary progressive MS PPMS. However, with time the vast majority of relapsing-remitting MS will convert to secondary progressive MS and experience relentless decline.

Typically this transition to the progressive phase of the disease begins in the late 40s and 50s. Around half of all people with MS develop cognitive impairments. In almost all cases, the disease becomes progressively worse with advancing fatigue, mental health problems, and brain fog.

As in other autoimmune diseases, people with MS seem to be at increased risk of metabolic dysregulation. In one small study, people with MS were almost three times as likely as healthy controls to have metabolic syndrome, and nearly half were insulin resistant. Another study found that people with MS were nearly 2.

How far along a person is in the unfolding of their disease may influence their risk level. SPMS is essentially stage two of the disease, where disability steadily worsens in people who previously had relapsing-remitting MS RRMS for years or decades.

In a third category, primary progressive PPMS , MS is progressive from the get-go, with no periods of remission. The study found insulin resistance in 74 percent of those with secondary progressive MS , compared with 39 percent of those with either RRMS or PPMS.

This effect may be driven by disease duration; participants with SPMS were diagnosed an average of 17 years before the study, whereas those with RRMS and PPMS were diagnosed 9 and 6 years prior, respectively. The researchers ruled out age as a possible confounding factor and noted that insulin resistance was most prevalent among those with the most severe symptoms.

Insulin resistance has also been linked to cognitive dysfunction in MS. A study that looked at 74 people with RRMS found that those with the highest fasting blood glucose levels struggled the most with tasks that required verbal memory, verbal fluency, executive function, and visuospatial processing.

The precise cause of MS remains unknown, but in the last decade, obesity in childhood or early adulthood has emerged as a possible environmental trigger. One leading theory for why this might be the case is that, besides stoking chronic inflammation , obesity disturbs the balance of adiponectin, leptin, and resistin—all of which have been seen in raised concentrations in people with MS.

But in severe cases, the disease can also increase the risk for cardiovascular events and all-cause mortality. This may be why the risk of having metabolic syndrome is twice as high in people with psoriasis compared to people without.

Type 1 diabetes is an autoimmune disease—in which the immune system attacks and destroys the insulin-producing β cells of the pancreas, forcing people with the condition to manage their own blood sugar by injecting insulin.

But over the past decade or so, new evidence has prompted some experts to ask whether Type 2 diabetes should be classed as an autoimmune disease too. There are. Do I think these autoimmune components are driving the disease? In and , Dr. First, they showed that blocking the action of T cells in obese mice prevented the animals from becoming insulin resistant.

Next, they showed that mice engineered to lack B cells were also protected from insulin resistance, even as they grew obese by eating a high-calorie, high-fat diet.

They treated another set of obese mice with an antibody called anti-CD20, which helps the body destroy mature B cells. Anti-CD20 is used to treat several autoimmune diseases, including rheumatoid arthritis and MS; in the obese mice, it kept their glucose levels in check. Finally, the researchers showed that overweight people with insulin resistance produce antibodies against some of their own proteins.

In contrast, other overweight people do not—suggesting an autoimmunity component to insulin resistance. Scientists are still exploring whether this is a secondary effect of Type 2 diabetes or whether autoimmunity is a true driver of the disease.

Some even suggest that Type 1 and Type 2 exist at opposite ends of a spectrum , where both autoimmunity and insulin resistance are governed by genetics and environmental factors. One thing is clear: Type 2 diabetes is fuelled by chronic low-grade inflammation , which influences everything from the onset to its unfolding complications.

In the years since the Winer brothers published those first papers implicating overactivity of B and T cells, other researchers have added to the picture of the inflammatory landscape in Type 2 diabetes.

For example, people with the disease often have inflammation in pancreatic cell groups called islets , characterized by a profusion of inflammatory cytokines, including TNF-α, IL-1β, and IL This sets up a vicious cycle of autoimmunity and metabolic dysregulation : diet-induced inflammation damages tissues, causing them to leak toxins; these cause the immune system to kick into overdrive and attack pancreatic β cells, impairing their ability to secrete insulin and exacerbating hyperglycemia, which drives insulin resistance and more inflammation.

Taken together, these findings are beginning to blur the lines between our traditional understanding of Type 1 and Type 2 diabetes. Poor metabolic health exacerbates autoimmune disease and can accelerate its complications.

Adding fuel to the fire, medications commonly prescribed to treat autoimmune diseases are known to induce hyperglycemia and can swiftly increase insulin resistance by an alarming degree. J Immunol. Rathmell JC , Farkash EA , Gao W , et al. IL-7 enhances the survival and maintains the size of naive T cells.

Saxton RA , Sabatini DM. mTOR signaling in growth, metabolism, and disease. Yang K , Shrestha S , Zeng Hu , et al. T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming.

Yang K , Neale G , Green DR , et al. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Lee K , Gudapati P , Dragovic S , et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways.

Wang R , Dillon CP , Shi LZ , et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.

Frauwirth KA , Riley JL , Harris MH , et al. The CD28 signaling pathway regulates glucose metabolism. Salmond RJ. mTOR regulation of glycolytic metabolism in T cells. Front Cell Dev Biol. Jacobs SR , Herman CE , Maciver NJ , et al. Glucose uptake is limiting in T cell activation and requires CDmediated Akt-dependent and independent pathways.

Nakaya M , Xiao Y , Zhou X , et al. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Integrative proteomics and phosphoproteomics profiling reveals dynamic signaling networks and bioenergetics pathways underlying T cell activation.

Klein Geltink RI , O'Sullivan D , Corrado M , et al. Mitochondrial priming by CD Ron-Harel N , Santos D , Ghergurovich JM , et al. Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation.

Cell Metabol. Luckheeram RV , Zhou R , Verma AD , et al. Clinical Dev Immunol. Macintyre AN , Gerriets VA , Nichols AG , et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.

Ray JP , Staron MM , Shyer JA , et al. The InterleukinmTORc1 Kinase axis defines the signaling, differentiation, and metabolism of T helper 1 and follicular B helper T cells. mTORC1 and mTORC2 kinase signaling and glucose metabolism drive follicular helper T cell differentiation.

Delgoffe GM , Kole TP , Zheng Y , et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Delgoffe GM , Pollizzi KN , Waickman AT , et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2.

Dang EV , Barbi J , Yang H-Yu , et al. Shehade H , Acolty V , Moser M , et al. Cutting edge: hypoxia-inducible factor 1 negatively regulates Th1 function. Peng M , Yin N , Chhangawala S , Xu K , Leslie CS , Li MO Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism.

Yang J-Qi , Kalim KW , Li Y , et al. RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. J Allergy Clin Immunol. Oestreich KJ , Read KA , Gilbertson SE , et al. Bcl-6 directly represses the gene program of the glycolysis pathway. Klysz D , Tai X , Robert PA , et al.

Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci Signal. Araujo L , Khim P , Mkhikian H , et al.

Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation. Choi S-C , Titov AA , Abboud G , et al. Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.

Nat Commun. Johnson MO , Wolf MM , Madden MZ , et al. Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism. Michalek RD , Gerriets VA , Jacobs SR , et al.

Basu S , Hubbard B , Shevach EM. Foxp3-mediated inhibition of Akt inhibits Glut1 glucose transporter 1 expression in human T regulatory cells. J Leukocyte Biol. Arvey A , Van Der Veeken J , Samstein RM , et al. Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells.

Angelin A , Gil-de-Gómez L , Dahiya S , et al. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Gerriets VA , Kishton RJ , Johnson MO , et al.

Foxp3 and Toll-like receptor signaling balance T reg cell anabolic metabolism for suppression. Eleftheriadis T , Pissas G , Karioti A , et al. Dichloroacetate at therapeutic concentration alters glucose metabolism and induces regulatory T-cell differentiation in alloreactive human lymphocytes.

J Basic Clin Physiol Pharm. De Rosa V , Galgani M , Porcellini A , et al. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants.

Kishore M , Cheung KCP , Fu H , et al. Regulatory T cell migration is dependent on glucokinase-mediated glycolysis. Weinberg SE , Singer BD , Steinert EM , et al. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Beier UH , Angelin A , Akimova T , et al.

FASEB J. Van Loosdregt J , Vercoulen Y , Guichelaar T , et al. Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Battaglia M , Stabilini A , Roncarolo M-G. Zeng Hu , Yang K , Cloer C , et al. mTORC1 couples immune signals and metabolic programming to establish T reg -cell function.

Sun Im-H , Oh M-H , Zhao L , et al. Watson MJ , Vignali PDA , Mullett SJ , et al. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Raynor JL , Chapman NM , Chi H. Metabolic control of memory T-cell generation and stemness.

Cold Spring Harb Perspect Biol. Han S-Ji , Glatman Zaretsky A , Andrade-Oliveira V , et al. White adipose tissue is a reservoir for memory T cells and promotes protective memory responses to infection. O'sullivan D. The metabolic spectrum of memory T cells. Immunol Cell Biol. Maekawa Y , Ishifune C , Tsukumo S-I , et al.

Nat Med. Dimeloe S , Mehling M , Frick C , et al. Brown EM , Kenny DJ , Xavier RJ. Gut microbiota regulation of T cells during inflammation and autoimmunity. Atarashi K , Suda W , Luo C , et al. Ectopic colonization of oral bacteria in the intestine drives T H 1 cell induction and inflammation.

Ivanov II , Atarashi K , Manel N , et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Tan TG , Sefik E , Geva-Zatorsky N , et al. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice.

Proc Natl Acad Sci USA. Viladomiu M , Kivolowitz C , Abdulhamid A , et al. IgA-coated E. coli enriched in Crohn's disease spondyloarthritis promote T H dependent inflammation.

Sci Transl Med. Zielinski CE , Mele F , Aschenbrenner D , et al. Pathogen-induced human TH17 cells produce IFN-γ or IL and are regulated by IL-1β. Teng F , Klinger CN , Felix KM , et al.

Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer's patch T follicular helper cells. Atarashi K , Tanoue T , Oshima K , et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.

Chai JN , Peng Y , Rengarajan S , et al. Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation. Sci Immunol. Hegazy AN , West NR , Stubbington MJT , et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway.

Mucosal Immunol. Kespohl M , Vachharajani N , Luu M , et al. Front Immunol. Microbiota metabolite butyrate differentially regulates Th1 and Th17 cells' differentiation and function in induction of colitis.

Inflamm Bowel Dis. Microbiota-derived short-chain fatty acids promote Th1 cell IL production to maintain intestinal homeostasis. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL production and gut immunity. Tan J , Mckenzie C , Vuillermin PJ , et al.

Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways.

Cell Rep. Arpaia N , Campbell C , Fan X , et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.

Smith PM , Howitt MR , Panikov N , et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Furusawa Y , Obata Y , Fukuda S , et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Bile acid metabolites control T H 17 and T reg cell differentiation.

cookielawinfo-checkbox-necessary 1 year Set by the GDPR Cookie Consent plugin, this cookie is used to record the user consent for the cookies in the "Necessary" category.

cookielawinfo-checkbox-others 1 year Set by the GDPR Cookie Consent plugin, this cookie is used to store the user consent for cookies in the category "Others". cookielawinfo-checkbox-performance 1 year Set by the GDPR Cookie Consent plugin, this cookie is used to store the user consent for cookies in the category "Performance".

It works only in coordination with the primary cookie. PHPSESSID session This cookie is native to PHP applications. The cookie is used to store and identify a users' unique session ID for the purpose of managing user session on the website.

The cookie is a session cookies and is deleted when all the browser windows are closed. It does not store any personal data. Functional functional. Functional cookies help perform certain functions, such as sharing the content of the website on social media platforms, collecting feedback and other third-party functions.

Cookie Duration Description bcookie 1 year LinkedIn sets this cookie from LinkedIn share buttons and ad tags to recognize browser ID. bscookie 1 year LinkedIn sets this cookie to store performed actions on the website. lang session LinkedIn sets this cookie to remember a user's language setting.

lidc 1 day LinkedIn sets the lidc cookie to facilitate data center selection. UserMatchHistory 1 month LinkedIn sets this cookie for LinkedIn Ads ID syncing. Performance performance. Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.

Analytics analytics. Analytical cookies are used to understand how visitors interact with the website. These cookies provide information on metrics such as number of visitors, bounce rate, traffic source, etc.

The cookie stores information anonymously and assigns a randomly generated number to recognize unique visitors. Some of the data that are collected include the number of visitors, their source, and the pages they visit anonymously. CONSENT 2 years YouTube sets this cookie via embedded youtube-videos and registers anonymous statistical data.

Advertisement advertisement. Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.

fr 3 months Facebook sets this cookie to show relevant advertisements to users by tracking user behaviour across the web, on sites that have Facebook pixel or Facebook social plugin.

IDE 1 year 24 days Google DoubleClick IDE cookies are used to store information about how the user uses the website to present them with relevant ads and according to the user profile.

net and is used to determine if the user's browser supports cookies. YSC session YSC cookie is set by Youtube and is used to track the views of embedded videos on Youtube pages.

yt-remote-connected-devices never YouTube sets this cookie to store the video preferences of the user using embedded YouTube video.

Energy metabolism maintains disseases activation Energy metabolism and autoimmune diseases intracellular and intercellular signal transduction, Low glycemic eating plays a crucial annd in immune response. Metabplism environmental stimulation, autoimkune cells change from resting to activation and trigger metabolic reprogramming. The immune system cells exhibit different metabolic characteristics when performing functions. The study of immune metabolism provides new insights into the function of immune cells, including how they differentiate, migrate and exert immune responses. Studies of immune cell energy metabolism are beginning to shed light on the metabolic mechanism of disease progression and reveal new ways to target inflammatory diseases such as autoimmune diseases, chronic viral infections, and cancer. Metabolic Dissases. Ultimate Guide. Studies megabolism that people with autoimmune conditions like MS and IBD are more likely to have diabetes and insulin resistance, but the links are not yet fully understood. Ceri Perkins. Kaitlin Sullivan. Terry Wahls, MD. Energy metabolism and autoimmune diseases

Energy metabolism and autoimmune diseases -

Lymphokine regulation of human lymphocyte proliferation: formation of resting G0 cells by removal of interleukin 2 in cultures of proliferating T lymphocytes. Cell Immunol. Lee J, Walsh MC, Hoehn KL, James DE, Wherry EJ, Choi Y.

Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity. Miguel L, Owen DM, Lim C, Liebig C, Evans J, Magee AI, et al. Goronzy JJ, Weyand CM. Developments in the scientific understanding of rheumatoid arthritis. Arthritis Res Ther.

Weyand CM, Fujii H, Shao L, Goronzy JJ. Rejuvenating the immune system in rheumatoid arthritis. Nat Rev Rheumatol. Jacob N, Jacob CO. Genetics of rheumatoid arthritis: an impressionist perspective.

Article PubMed Google Scholar. Schaller M, Burton DR, Ditzel HJ. Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease.

Ukaji F, Kitajima I, Kubo T, Shimizu C, Nakajima T, Maruyama I. Ann Rheum Dis. Saulot V, Vittecoq O, Charlionet R, Fardellone P, Lange C, Marvin L, et al.

Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients with early rheumatoid arthritis. Arthritis Rheum. Balakrishnan L, Bhattacharjee M, Ahmad S, Nirujogi RS, Renuse S, Subbannayya Y, et al.

Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients. Clin Proteomics. Yang Z, Fujii H, Mohan SV, Goronzy JJ, Weyand CM. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. Lee K, Won HY, Bae MA, Hong JH, Hwang ES.

Gelderman KA, Hultqvist M, Olsson LM, Bauer K, Pizzolla A, Olofsson P, et al. Rheumatoid arthritis: the role of reactive oxygen species in disease development and therapeutic strategies. Antioxid Redox Signal. Pizzolla A, Wing K, Holmdahl R.

Am J Pathol. Yang Z, Goronzy JJ, Weyand CM. Aging, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity — catalysts of autoimmunity and chronic inflammation.

Weyand CM, Fulbright JW, Goronzy JJ. Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol. Goronzy JJ, Li G, Yang Z, Weyand CM. The janus head of T cell aging — autoimmunity and immunodeficiency. Front Immunol. Weyand CM, Yang Z, Goronzy JJ.

T-cell aging in rheumatoid arthritis. Curr Opin Rheumatol. Fujii H, Shao L, Colmegna I, Goronzy JJ, Weyand CM. Telomerase insufficiency in rheumatoid arthritis. Shao L, Fujii H, Colmegna I, Oishi H, Goronzy JJ, Weyand CM. Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis.

Schmidt D, Goronzy JJ, Weyand CM. J Clin Invest. Li G, Yu M, Lee WW, Tsang M, Krishnan E, Weyand CM, et al. Decline in miRa expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat Med. Yu M, Li G, Lee WW, Yuan M, Cui D, Weyand CM, et al.

Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. Wahl DR, Petersen B, Warner R, Richardson BC, Glick GD, Opipari AW. Characterization of the metabolic phenotype of chronically activated lymphocytes.

Gergely Jr P, Grossman C, Niland B, Puskas F, Neupane H, Allam F, et al. Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus.

Perl A. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment.

Doherty E, Oaks Z, Perl A. Increased mitochondrial electron transport chain activity at complex I is regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus erythematosus.

Kato H, Perl A. Fernandez D, Bonilla E, Mirza N, Niland B, Perl A. Rapamycin reduces disease activity and normalizes T cell activation-induced calcium fluxing in patients with systemic lupus erythematosus.

Lai ZW, Hanczko R, Bonilla E, Caza TN, Clair B, Bartos A, et al. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial.

Wu T, Xie C, Han J, Ye Y, Weiel J, Li Q, et al. Metabolic disturbances associated with systemic lupus erythematosus. PLoS One. McDonald G, Deepak S, Miguel L, Hall CJ, Isenberg DA, Magee AI, et al.

Sarchielli P, Greco L, Floridi A, Gallai V. Excitatory amino acids and multiple sclerosis: evidence from cerebrospinal fluid. Arch Neurol. Tisell A, Leinhard OD, Warntjes JB, Aalto A, Smedby O, Landtblom AM, et al. Increased concentrations of glutamate and glutamine in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans.

Marchetti P, Ranelletti FO, Natoli V, Sica G, De Rossi G, Iacobelli S. Presence and steroid inducibility of glutamine synthetase in human leukemic cells.

J Steroid Biochem. Download references. This work was partially supported by grants from the National Institutes of Health R01 AR, R01 AI, P01 HL, R01 AI, R01 HL, and R01 AG ZY received fellowship support from the Govenar Discovery Fund.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Department of Medicine, Stanford University School of Medicine, CCSR Building Rm , Campus Drive West, Stanford, CA, , USA.

Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN, , USA. You can also search for this author in PubMed Google Scholar.

Correspondence to Cornelia M Weyand. Reprints and permissions. Yang, Z. et al. T-cell metabolism in autoimmune disease. Arthritis Res Ther 17 , 29 Download citation. Published : 11 February Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Skip to main content. Search all BMC articles Search. Download PDF. Abstract Cancer cells have long been known to fuel their pathogenic growth habits by sustaining a high glycolytic flux, first described almost 90 years ago as the so-called Warburg effect.

Introduction More than 90 years ago, physician-scientist Otto Warburg proposed that cancer is, in principle, a metabolic disease characterized by a mitochondrial defect that shifts energy production towards glycolysis [ 1 ]. Metabolic regulation of normal immune responses To protect the host from infections and malignancies, immune cells need to respond promptly to antigens and danger signals, including massive expansion of T cells and B cells, migration of cells to relevant tissue sites, and synthesis of cytokines and effector molecules.

Figure 1. Full size image. Table 1 Dominant metabolic pathways in resting and activated T cells Full size table.

Table 2 Disease-specific metabolic abnormalities in rheumatoid arthritis and systemic lupus erythematosus Full size table. Metabolic regulation of pathogenic immune responses Rheumatoid arthritis Rheumatoid arthritis RA is a prototypic autoimmune disease, characterized by persistent immune activation [ 31 , 32 ].

Figure 2. Figure 3. Conclusions Highly proliferative immune cells share with cancer cells the switch to progrowth glycolysis, which secures both ATP and macromolecules. References Warburg O. CAS PubMed Google Scholar Hotamisligil GS.

Article CAS PubMed Google Scholar Warburg O, Gawehn K, Geissler AW. CAS PubMed Google Scholar Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, et al. Article CAS PubMed Google Scholar Sinclair LV, Rolf J, Emslie E, Shi YB, Taylor PM, Cantrell DA.

Article PubMed Central CAS PubMed Google Scholar Bental M, Deutsch C. Article CAS PubMed Google Scholar Kovacs B, Maus MV, Riley JL, Derimanov GS, Koretzky GA, June CH, et al.

Article PubMed Central CAS PubMed Google Scholar Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al. Article PubMed Central CAS PubMed Google Scholar Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, et al. Article PubMed Central CAS PubMed Google Scholar Gaber T, Schellmann S, Erekul KB, Fangradt M, Tykwinska K, Hahne M, et al.

Article CAS PubMed Google Scholar Gaber T, Tran CL, Schellmann S, Hahne M, Strehl C, Hoff P, et al.

Article CAS PubMed Google Scholar Goronzy JJ, Shao L, Weyand CM. Article PubMed Central PubMed Google Scholar Caro-Maldonado A, Wang R, Nichols AG, Kuraoka M, Milasta S, Sun LD, et al. Article PubMed Central CAS PubMed Google Scholar Greiner EF, Guppy M, Brand K.

CAS PubMed Google Scholar Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, et al. Article PubMed Central CAS PubMed Google Scholar Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. Article PubMed Central CAS PubMed Google Scholar Dufort FJ, Gumina MR, Ta NL, Tao Y, Heyse SA, Scott DA, et al.

Article PubMed Central CAS PubMed Google Scholar van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, et al. Article PubMed Central PubMed Google Scholar Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, et al.

Article PubMed Central CAS PubMed Google Scholar Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, et al. Article PubMed Central CAS PubMed Google Scholar Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, et al. Article PubMed Central CAS PubMed Google Scholar Ardawi MS.

Article CAS PubMed Google Scholar Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, Cheng X, et al. Article PubMed Central CAS PubMed Google Scholar DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, et al.

Article PubMed Central CAS PubMed Google Scholar Robichaud PP, Boulay K, Munganyiki JE, Surette ME. Article PubMed Central PubMed Google Scholar Bettens F, Kristensen F, Walker C, Bonnard GD, de Weck AL.

Article CAS PubMed Google Scholar Lee J, Walsh MC, Hoehn KL, James DE, Wherry EJ, Choi Y. Article PubMed Central CAS PubMed Google Scholar Miguel L, Owen DM, Lim C, Liebig C, Evans J, Magee AI, et al.

Article CAS PubMed Google Scholar Goronzy JJ, Weyand CM. Article PubMed Central PubMed Google Scholar Weyand CM, Fujii H, Shao L, Goronzy JJ. Article CAS PubMed Google Scholar Jacob N, Jacob CO. Article PubMed Google Scholar Schaller M, Burton DR, Ditzel HJ.

Article CAS PubMed Google Scholar Ukaji F, Kitajima I, Kubo T, Shimizu C, Nakajima T, Maruyama I. Article PubMed Central CAS PubMed Google Scholar Saulot V, Vittecoq O, Charlionet R, Fardellone P, Lange C, Marvin L, et al. Article CAS PubMed Google Scholar Balakrishnan L, Bhattacharjee M, Ahmad S, Nirujogi RS, Renuse S, Subbannayya Y, et al.

Article PubMed Central PubMed Google Scholar Yang Z, Fujii H, Mohan SV, Goronzy JJ, Weyand CM. Article PubMed Central CAS PubMed Google Scholar Lee K, Won HY, Bae MA, Hong JH, Hwang ES. The main housekeeping functions that use significant amounts of ATP are processes of ion transport and macromolecule synthesis.

Specific immune functions include motor functions, antigen processing and presentation, activation and effector functions such as synthesis of antibodies, cytotoxicity, and regulatory functions [ 1 ] Table 1.

Calculations show that a quiescent leukocyte needs 1. Activation of quiescent leukocytes leads to an increase of energy expenditure by a factor of 1. The cellular energy metabolism is relevant to be considered in terms of diseases, for example in cells within the inflamed rheumatoid arthritic joint, because energy supply is limited [ 27 , 28 ].

Secondly, cell accumulation and inflammatory edema increase the distance between cells and oxygen-supplying arterial vessels. Thirdly, vasodilatation, as induced by inflammatory mediators such as prostaglandin E 2 , lowers blood flow and thus the supply of oxygen and nutrients is reduced such as glucose and amino acids as well as the removal of metabolic waste such as lactate and carbon dioxide [ 27 , 28 ].

Furthermore, specific T-cell functions such as cytokine production and proliferation are unaffected in glucose-containing medium, even under complete OXPHOS suppression.

Only when glucose is also absent are these functions significantly decreased [ 29 ]. These observations support the view of hypoxia being a key driving factor in chronic inflammation.

The first data indicating the hypoxic nature of the rheumatoid arthritis RA synovium were achieved in the s by measuring oxygen tension by means of a Clark-type electrode in samples of synovial fluids of patients with RA [ 28 , 30 , 31 ].

Hypoxia has been demonstrated in patients with RA undergoing surgery for tendon rupture by Sivakumar and colleagues [ 32 ]. Just recently, by means of a novel oxygen-sensing probe in vivo , even a direct relationship between tissue partial pressure of oxygen levels and joint inflammation specifically T-cell and macrophage infiltrates and proinflammatory cytokine expression could be demonstrated for the first time [ 33 ], and it was shown that hypoxia can be reversed by antiinflammatory treatment [ 34 ].

One principal regulator of the adaptive response to hypoxia is the transcription factor hypoxia inducible factor HIF -1 [ 28 , 35 ]. HIF-1 is a heterodimeric protein that consists of an oxygen-sensitive α subunit and a constitutively expressed β subunit [ 28 , 36 ]. In nonhypoxic cells, HIF-1α is continuously tagged by oxygen-dependent hydroxylation and in this way targeted for proteasomal degradation [ 28 , 36 ].

Under hypoxic conditions, however, HIF-1 is stabilized. HIF target genes promote erythropoiesis, angiogenesis and vasodilatation, and HIF is a master switch to a glycolytic cell metabolism, resolving and counteracting hypoxic conditions [ 28 ].

Several findings indicate that HIF is involved in the persistence of inflammation and progression of neovascularization during RA.

HIF is abundantly expressed in the arthritic tissue [ 38 ]. Deletion of HIF in macrophages and neutrophils resulted in a complete loss of the inflammatory response [ 39 ]. Hypoxia might also play a central role in pathogenesis of systemic sclerosis by augmenting vascular disease and tissue fibrosis [ 40 , 41 ].

However, HIF-1 was found to be decreased in the epidermis of systemic sclerosis patients compared with healthy controls [ 42 ], perhaps due to an increased prolyl-hydroxylase activity resulting in faster degradation of HIF-1 [ 41 ].

Hypoxia, and specifically HIF-1, is a potent and rapid inducer of MIF. MIF is also able to counter-regulate glucocorticoid-mediated suppression of MIF and HIF-1α expression [ 36 ].

Targeting MIF and HIF may thus be effective in disrupting self-maintaining inflammation. The differentiation of naïve CD4 cells into Th1 and Th17 subsets of T-helper cells is selectively regulated by signaling from mTORC1 that is dependent on the small GTPase Rheb [ 43 ].

Th1, Th2 and Th17 cells express high surface levels of the glucose transporter- Glut1 and switch on a highly glycolytic program. In contrast, regulatory T cells Tregs express low levels of Glut1 and have high lipid oxidation rates [ 44 ]. In an asthma model, AMPK stimulation was sufficient to decrease Glut1 and increase Treg generation, indicating that the distinct metabolic programs can be modulated in vivo [ 44 ].

Recently, persistent hypoxia and glycolysis were demonstrated to control the balance between inflammation-promoting Th17 cells and inflammation-restricting Tregs [ 9 , 45 ]. Hypoxia-induced HIF expression exerts a direct transcriptional activation of RORγt, a master regulator of Th17 cell differentiation, and recruitment to the IL promoter via tertiary complex formation with RORγt and p Figure 1 [ 9 , 45 ].

Concurrently, HIF-1 attenuates induced Treg development by binding Foxp3, a key transcription factor that promotes the Treg lineage, via a proposed ubiquitination pathway [ 9 , 45 ].

Mice with HIF-1α-deficient T cells are resistant to induction of Thdependent experimental autoimmune encephalitis, associated with diminished Th17 cells and increased Tregs, indicating the therapeutic potential of HIF modulation.

Similar to these findings, another study suggested that HIF-1α is involved in differentiation of Th17 cells and Tregs, but ascribed the role of HIF-1a to upregulation of glycolysis and not as a direct effect of HIF-1a on RORγt and Foxp3 [ 9 , 46 ].

Tumor hypoxia appears to be different, as it has been reported to inhibit T-cell proliferation and cytokine secretion and to activate Tregs [ 48 ].

Glycolysis has been suggested to play a role in the pathogenesis of RA [ 49 ]. The activity levels of two major enzymes of the glycolytic pathway - glyceraldehyde 3-phosphate dehydrogenase and lactate dehydrogenase - were increased in RA synovial cells [ 50 ].

However, clear studies of a direct relationship of increased glycolytic activity and inflammation are lacking. It is striking that several glycolytic enzymes such as glucosephosphate isomerase, enolase, aldolase and triose phosphate isomerase act as autoantigens [ 49 ]; however, their role in RA remains unclear [ 49 , 51 , 52 ].

Rapamycin also known as sirolimus is an mTOR inhibitor used in transplantation medicine. This inhibitor acts similar to the immunosuppressant FK tacrolimus by binding to the intracellular immunophilin FK-binding protein 12 FKBP Unlike the FKFKBP12 complex that inhibits calcineurin, however, the rapamycin-FKBP12 complex interferes with the function of mTOR.

Rapamycin has been found effective for systemic lupus erythematosus and systemic sclerosis in animal models and pilot clinical trials [ 53 — 57 ].

Tregs can be expanded by rapamycin in vitro [ 58 ] and were found to suppress colitis in an experimental mouse model [ 59 ].

Treatment of mice after infection with either the mTOR inhibitor rapaymcin or the AMPK stimulator metformin, two drugs that augment fatty acid oxidation, enhanced the development of memory CD8 T cells [ 6 , 60 , 61 ]. Similar to T cells, dendritic cells were recently shown upon activation by Toll-like receptors to switch from oxidative phosphorylation to glycolysis [ 62 ].

Activation of macrophages by IFNγ and lipopolysaccharide inhibits mitochondrial respiration by release of large quantities of nitric oxide produced by the inducible nitric oxide synthase [ 65 ]. Furthermore, monocytes begin to acquire a glycolytic metabolism during differentiation into macrophages, with possible significance for the ability of tissue macrophages to adapt to hypoxia [ 66 ].

Prolongation of survival by hypoxia has also been found for human neutrophils [ 67 , 68 ]. NOD-like receptors are involved in the recognition of host-derived and microbial danger-associated molecules that lead to the assembly of high-molecular-mass complexes called inflammasomes and the subsequent generation- of active caspase 1, a requisite for the production of the inflammatory cytokine IL-1β [ 7 ].

Recently, the NLRP3 inflammasome has been shown to cause insulin resistance in the periphery and may be important for the pathogenesis of type 2 diabetes [ 7 , 69 ]. In contrast to metabolic changes, which occur locally in cells and tissue - for example, due to hypoxia at the site of inflammation - interesting metabolic changes can also occur systemically.

Circulating peripheral blood cells, such as T cells, display oxidative stress due to depletion of glutathione in systemic lupus erythematosus [ 70 ]. Levels of surface thiols and intracellular glutathione of leukocytes are significantly lower in RA patients [ 71 ].

Excessive production of reactive oxygen species disturbs the redox status and can modulate the expression of inflammatory chemokines, leading to inflammatory processes [ 72 ]. Such differences in metabolism may represent a clear distinction between localized and systemic autoimmune inflammatory diseases.

Energy metabolism is not only a question for a single cell or a group of cells such as, for example, T cells or muscle cells, because provision and allocation of energy-rich fuels involves the entire body. Need for energy-rich substrates at a certain location in the body can induce a systemic response if local stores are not sufficient to provide necessary supplies.

The systemic response redirects energy-rich fuels from stores to the site of action, the consumers [ 2 ]. Such a redirection program can be started by a voluntary act when an individual decides to use muscles during exercise. In such a situation, the central nervous system activates, among others, the sympathetic nervous system adrenaline, noradrenaline , the hypothalamic-pituitary-adrenal axis cortisol , and the hypothalamic-pituitary-somatic axis growth hormone, insulin-like growth factor-1 , which induce gluconeogenesis,- glycogenolysis, and lipolysis.

This is supported by release of IL-6 from muscles into systemic circulation, which helps activate the redirection program [ 73 ]. Redirection of energy-rich substrates from storage sites to consumer can be called the energy appeal reaction.

If the immune system needs energy-rich fuels in the context of infection or other forms of activation, a similar energy appeal reaction is prompted [ 2 ]. The response is a concerted action of the neuroendocrine immune network.

But does the activated immune system need a lot of energy? Table 2 presents the energy demand of the entire body, systems, and organs.

Obviously, the immune system needs a lot of energy, particularly in an activated state. In an inflammatory situation, the energy appeal reaction is driven by cytokine-induced stimulation of the central nervous system, endocrine organs, and energy storage organs such as the liver, muscles, and fat tissue [ 2 ].

IL-6 is a classical candidate that can activate these remote places but also IFNγ, IFNα, IL-2, TNF, and others [ 2 ]. The question remains whether this seemingly adaptive program has been positively selected in the context of CIDs such as RA or systemic lupus erythematosus.

The evolutionary principle of replication with variation and selection is undeniably fundamental and has history. This is a successful history of positive selection, which can only happen under circumstances of unrestricted gene transfer to offspring.

The hypothesis is that genes which play a specific role in CIDs were not positively and specifically selected for a CID because unrestricted gene transfer was not possible in CIDs [ 2 , 74 ]. If this is correct, regulatory mechanisms of the neuroendocrine immune network did not evolve to cope with CIDs.

Instead, the neuroendocrine immune network was positively selected in the context of nonlife-threatening transient inflammatory episodes such as, for example, infection or wound healing.

These episodes are usually short lived and do not last longer than 3 to 6 weeks. No prolonged adaptive program specifically exists for CIDs. Similarly, the abovementioned energy appeal reaction as a consequence of systemic cytokine stimulation has been positively selected for transient nonlife-threatening inflammatory episodes [ 2 , 74 ].

Furthermore, genes that are associated with CIDs have been positively selected independent of CIDs. The theory of antagonistic pleiotropy - formulated by Williams in the s - similarly applies to CIDs [ 2 , 75 ]. This theory suggests that genes associated with CIDs have been positively selected to improve survival at younger ages and to stimulate reproduction independent of CIDs.

Recent delineation shows that several CID risk genes have a pleiotropic meaning outside CIDs at younger ages [ 76 ]. Organisms evolved under conditions that favored the development of complex mechanisms for obtaining food and for storage and allocation of energy-rich fuels.

Energy regulation and cellular bioenergetics take the highest position in the hierarchy of homeostatic control. We can call them storing factors.

In contrast, provision of energy-rich fuels to the entire body in the form of glucose, protein, and fatty acids is mainly supported by mediator substances of the sympathetic nervous system, the hypothalamic-pituitary-hormonal axes cortisol and growth hormone , and the pancreas glucagon.

We can call them provision factors. Table 3 describes particular aspects of the neuroendocrine immune response linking it to the energy appeal reaction. The energy appeal reaction is not an unspecific fight-or-flight response in the sense of Hans Selye, but an adaptive program.

If the adaptive program is used too long, real problems can appear that are a consequence of worn-out regulation. That exhausted regulation really exists is substantiated by the fact that patients on ICUs with severe activation of the stress system sometimes suffer from lifelong adrenal insufficiency even after overall recovery [ 77 ].

A longstanding reallocation program can thus lead to acute and chronic disease sequelae as mentioned in Table 3. The framework explains that CID sequelae are a consequence of a continuous energy appeal reaction. The systemic response of the body - the energy appeal reaction - is important to support the immune system during short-lived inflammatory episodes, but its continuous use in CIDs is highly unfavorable.

Since disease sequelae are a significant part of clinical CID, etiology of disease sequelae is also part of CID etiology. It becomes understandable that long-term changes of the neuroendocrine immune network as a consequence of a chronic energy appeal reaction are also part of etiological considerations.

We conclude that among genetic issues, environmental factors microbes, toxins, drugs, injuries, radiation, cultural background, and geography , exaggerated immune and wound responses, and irrecoverable tissue destruction, changes of the neuroendocrine immune network in the context of a prolonged energy appeal reaction become a fifth factor of CID etiology [ 78 ].

Metabolic pathways drive an energy appeal reaction for the immune response on cellular and organism levels. However, if the immune response is not sufficient to resolve inflammation, the metabolic programs can support ongoing chronic inflammation and lead to metabolic disease sequelae.

This suggests chronic inflammation to be powered by energy metabolism, indicating that energy metabolism is a promising therapeutic target. Buttgereit F, Burmester GR, Brand MD: Bioenergetics of immune functions: fundamental and therapeutic aspects.

Immunol Today. Article CAS PubMed Google Scholar. Straub RH, Cutolo M, Buttgereit F, Pongratz G: Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med. Finlay D, Cantrell DA: Metabolism, migration and memory in cytotoxic T cells.

Nat Rev Immunol. Article PubMed Central CAS PubMed Google Scholar. Fox CJ, Hammerman PS, Thompson CB: Fuel feeds function: energy metabolism and the T-cell response. Mathis D, Shoelson SE: Immunometabolism: an emerging frontier.

Pearce EL: Metabolism in T cell activation and differentiation. Curr Opin Immunol. Tannahill GM, O'Neill LA: The emerging role of metabolic regulation in the functioning of Toll-like receptors and the NOD-like receptor Nlrp3. FEBS Lett. Inoki K, Kim J, Guan KL: AMPK and mTOR in cellular energy homeostasis and drug targets.

Annu Rev Pharmacol Toxicol. Nutsch K, Hsieh C: When T cells run out of breath: the HIF-1α story. Powell JD, Pollizzi KN, Heikamp EB, Horton MR: Regulation of immune responses by mTOR. Annu Rev Immunol. Article PubMed Central PubMed Google Scholar. Procaccini C, Galgani M, De Rosa V, Matarese G: Intracellular metabolic pathways control immune tolerance.

Trends Immunol. Gatza E, Wahl DR, Opipari AW, Sundberg TB, Reddy P, Liu C, Glick GD, Ferrara JL: Manipulating the bioenergetics of alloreactive T cells causes their selective apoptosis and arrests graft-versus-host disease.

Sci Transl Med. Jones RG, Thompson CB: Revving the engine: signal transduction fuels T cell activation. Vander Heiden MG, Cantley LC, Thompson CB: Understanding the Warburg effect: the metabolic requirements of cell proliferation.

Summers SA, Yin VP, Whiteman EL, Garza LA, Cho H, Tuttle RL, Birnbaum MJ: Signaling pathways mediating insulin-stimulated glucose transport. Nature ; 78— Forero-Peña DA, Gutierrez FRS. Statins as modulators of regulatory T-cell biology.

Mediat Inflamm ; Zeiser R. Immune modulatory effects of statins. Immunology ; 69— Procaccini C, Carbone F, Galgani M, et al. Obesity and susceptibility to autoimmune diseases.

Expert Rev Clin Immunol ; 7: — Arai S, Maehara N, Iwamura Y, et al. Obesity-associated autoantibody production requires AIM to retain the immuno-globulin M immune complex on follicular dendritic cells. Cell Rep ; 3: — Winer DA, Winer S, Shen L, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies.

Nat Med ; —7. Francisco V, Pino J, Campos-Cabaleiro V, et al. Obesity, fat mass and immune system: role for leptin.

Front Physiol ; 9: Procaccini C, Pucino V, Mantzoros CS, Matarese G. Leptin in autoimmune diseases. Metabolism ; 92— Neumann E, Hasseli R, Ohl S, Lange U, Frommer KW, Müller-Ladner U. Adipokines and autoimmunity in inflammatory arthritis. Cells ; Neiman M, Hellström C, Just D, et al.

Individual and stable autoantibody repertoires in healthy individuals. Autoimmunity ; 1— Petta I, Fraussen J, Somers V, Kleinewietfeld M.

Interrelation of diet, gut microbiome, and autoantibody production. Front Immunol ; 9: Tsigalou C, Vallianou N, Dalamaga M. Autoantibody production in obesity: is there evidence for a link between obesity and autoimmunity?

Curr Obes Rep ; 9: — B cells in the pathophysiology of myasthenia gravis. Muscle Nerve ; — B lymphocytes in neuromyelitis optica.

Neurol Neuroimmunol Neuroinflamm ; 2: e Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol ; — Felton JL, Maseda D, Bonami RH, Hulbert C, Thomas JW. Anti-insulin B cells are poised for antigen presentation in type 1 diabetes.

Hulbert C, Riseili B, Rojas M, Thomas JW. B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice.

J Immunol ; —8. Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Immunol Rev ; 90— Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev ; — Stefan N, Kantartzis K, Machann J, et al.

Identification and characterization of metabolically benign obesity in humans. Arch Intern Med ; — Frasca D, Diaz A, Romero M, Vazquez T, Blomberg BB. Obesity induces pro-inflammatory B cells and impairs B cell function in old mice. Mech Ageing Dev ; 91—9. Frasca D, Diaz A, Romero M, Thaller S, Blomberg BB.

Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. PLoS One ; e Ferrara CT, Geyer SM, Liu YF, et al. Excess BMI in childhood: a modifiable risk factor for type 1 diabetes development? Diabetes Care ; — Fourlanos S, Harrison LC, Colman PG.

The accelerator hypothesis and increasing incidence of type 1 diabetes. Curr Opin Endocrinol Diabetes Obes ; —5. Fourlanos S, Varney MD, Tait BD, et al. The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes.

Diabetes Care ; —9. Download references. Environmental Medicine, Poznan University of Medical Sciences, Fredry 10, , Poznan, Poland. Institute of Human Genetics, Polish Academy of Science, Strzeszynska 32, , Poznan, Poland.

Hypertension, Angiology and Internal Medicine, Poznan University of Medical Sciences, Fredry 10, , Poznan, Poland.

Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Fredry 10, , Poznan, Poland. You can also search for this author in PubMed Google Scholar. Correspondence to Jacek Karczewski.

Financial support: The work was supported by the START Program of the Foundation for Polish Science FNP granted to Aleksandra Zielinska. Conflict of interest: none. Karczewski, J. et al. Metabolic link between obesity and autoimmune diseases.

Eur Cytokine Netw 32 , 64—72 Download citation. Accepted : 17 December Published : 11 February Issue Date : December Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Abstract The abnormal accumulation of visceral adipose tissue in obesity is associated with metabolic changes that include altered glucose tolerance, insulin resistance, hyperlipidemia, and metabolic syndrome.

Access this article Log in via an institution. References Lee GR. Article PubMed Central Google Scholar MacIver NJ, Michalek RD, Rathmell JC. Article CAS PubMed PubMed Central Google Scholar Cooper GS, Bynum ML, Somers EC.

Article PubMed PubMed Central Google Scholar Theofilopoulos AN, Kono DH, Baccala R. Article CAS PubMed PubMed Central Google Scholar Lerner A, Jeremias P, Matthias T. Article Google Scholar Ehlers S, Kaufmann SH, Participants of the 99 th Dahlem Conference..

Article CAS PubMed Google Scholar Bach JF. Article PubMed Google Scholar De Rosa V, La Cava A, Matarese G. Article CAS PubMed Google Scholar Economic Research Service ERS. Article PubMed PubMed Central Google Scholar Jackson SE, Llewellyn CH, Smith L.

Article PubMed PubMed Central Google Scholar Harpsøe MC, Basit S, Andersson M, et al. Article PubMed Google Scholar Gremese E, Tolusso B, Gigante MR, Ferraccioli G. Article PubMed PubMed Central Google Scholar Jensen CB, Ängquist LH, Mendall MA, Sørensen TIA, Baker JL, Jess T. Article PubMed Google Scholar Odegaard JI, Chawla A.

Article Google Scholar Mokry LE, Ross S, Timpson NJ, Sawcer S, Davey Smith G, Richards JB. Article PubMed PubMed Central Google Scholar Sterry W, Strober BE, Menter A, International Psoriasis Council.

Article CAS PubMed Google Scholar Sikaris KA. PubMed PubMed Central Google Scholar Karczewski J, Sledzinska E, Baturo A, et al. Article CAS PubMed Google Scholar Reilly SM, Saltiel AR. Article CAS PubMed Google Scholar Whiteside SK, Snook JP, Williams MA, Weis JJ.

Article CAS PubMed PubMed Central Google Scholar Lercher A, Baazim H, Bergthaler A. Article CAS PubMed PubMed Central Google Scholar Efeyan A, Comb WC, Sabatini DM. Article Google Scholar Saxton RA, Sabatini DM. Article CAS PubMed PubMed Central Google Scholar Chi H. Article CAS PubMed PubMed Central Google Scholar Kolan SS, Li G, Wik JA, et al.

Article CAS PubMed Google Scholar Bantug GR, Galluzzi L, Kroemer G, Hess C. Article CAS PubMed Google Scholar Winer S, Chan Y, Paltser G, et al.

Article CAS PubMed PubMed Central Google Scholar Feuerer M, Herrero L, Cipolletta D, et al. Article CAS PubMed PubMed Central Google Scholar Nishimura S, Manabe I, Nagasaki M, et al.

Article CAS PubMed Google Scholar Zúñiga LA, Shen WJ, Joyce-Shaikh B, et al. Article PubMed Google Scholar Yang H, Youm YH, Vandanmagsar B, et al. Article CAS PubMed Google Scholar Blagih J, Coulombe F, Vincent EE, et al. Article CAS PubMed Google Scholar Stentz FB, Kitabchi AE.

Article CAS PubMed Google Scholar Martinez N, Vallerskog T, West K, et al. Article CAS PubMed Google Scholar Chen S, Feng B, George B, Chakrabarti R, Chen M, Chakrabarti S. Article CAS PubMed Google Scholar Deb DK, Chen Y, Sun J, Wang Y, Li YC. Article CAS PubMed Google Scholar Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M.

Article CAS PubMed Google Scholar Eguchi K, Manabe I, Oishi-Tanaka Y, et al. Article CAS PubMed Google Scholar Cluxton D, Petrasca A, Moran B, Fletcher JM.

Article CAS PubMed PubMed Central Google Scholar Haghikia A, Jörg S, Duscha A, et al. Article CAS PubMed Google Scholar Endo Y, Asou HK, Matsugae N, et al.

Article CAS PubMed Google Scholar Mauro C, Smith J, Cucchi D, et al. Article CAS PubMed PubMed Central Google Scholar Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MAR.

Article Google Scholar Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula SJ. Article CAS PubMed Google Scholar Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A.

Article CAS PubMed Google Scholar Cipolletta D, Feuerer M, Li A, et al. Article CAS PubMed PubMed Central Google Scholar Wu D, Han JM, Yu X, et al. Article CAS PubMed Google Scholar Li C, Spallanzani RG, Mathis D. Article CAS PubMed Google Scholar Delgoffe GM, Pollizzi KN, Waickman AT, et al.

Article CAS PubMed PubMed Central Google Scholar Stelzner K, Herbert D, Popkova Y, et al. Article CAS PubMed Google Scholar Lu L, Barbi J, Pan F.

Gut microbiota affects Energu cell responses by providing a series of antigens and autoimmun. In metaoblism review, we describe Energy metabolism and autoimmune diseases Matcha green tea for skin metabolic programs in different Natural herb remedies cell subsets, provide evidence of T cell metabolism metabolissm by gut microbiota, explore the T cell metabolic autoimmunw in metabolissm disorders, atoimmune discuss the Energy metabolism and autoimmune diseases behind T cell metabolism-related approaches to treat autoimmune disorders. Glycolysis is the process that breaks glucose into pyruvate by a series of enzymes in the cytoplasm. Subsequently, glucose-derived pyruvate can be either metabolized to lactate, which is excreted from the cell or converted to acetyl coenzyme A acetyl-CoAand enters the tricarboxylic acid TCA cycle to generate reducing equivalents NADH and FADH 2 for OXPHOS by delivering electrons to the electron transport chain in mitochondria. Therefore, glucose provides energy to cells through both glycolysis and OXPHOS. Besides glucose, fatty acids and glutamine can also be metabolized to acetyl-CoA and α-ketoglutarate via fatty acid oxidation β-oxidation and glutaminolysis, respectively. These substrates are recruited to the TCA cycle and generate ATP through OXPHOS.

Video

This is what happens when you have an autoimmune disease

Author: Tarisar

0 thoughts on “Energy metabolism and autoimmune diseases

Leave a comment

Yours email will be published. Important fields a marked *

Design by ThemesDNA.com