ReviewObesity in autoimmune diseases: Not a passive bystander
Introduction
For several decades, industrialized countries face an increased prevalence of immune-mediated diseases [1], [2]. Most of these inflammatory conditions result from a complex interaction between genetic background and multiple environmental factors [3], [4], [5], [6], [7], [8]. Since genetic basis has remained constant over time, there is increasing recognition that environmental factors, especially the Western lifestyle, have a preponderant role in this growing prevalence [9]. Westernization is accompanied by profound changes in dietary habits, promoting high-fat, high-sugar, high-salt foods [10] with excess calorie intake, leading to obesity outbreak over the past 20 years [11], [12]. Therefore, the links between obesity and autoimmunity were questioned and the involvement of obesity in the rise of autoimmune conditions was strongly suggested. This link became even more fascinating in recent years since the discovery of the remarkable properties of adipose tissue. Indeed, the white adipose tissue (WAT), long regarded as an inert energy storage tissue, has been recognized to be an essential endocrine organ, secreting a wide variety of soluble mediators termed “adipokines” or “adipocytokines” [13]. Initially identified for their metabolic and appetite regulation activities, adipokines are known to be involved in various processes including immunity and inflammation [14]. By their pro-inflammatory action, these molecules contribute to the so-called “low-grade inflammatory state” in obese subjects, resulting in a cluster of comorbidities such as metabolic syndrome, diabetes, or cardiovascular complications [13]. On this basis, it is now of major interest to clarify the relationship between obesity and autoimmune/inflammatory diseases. In this review, following a short overview of the main mechanisms highlighted so far to link obesity and autoimmunity, we will detail metabolic and immunological activities of the main adipokines. Then, we shall focus on obesity and more precisely adipokines involvement, in the development and prognosis of several immune-mediated conditions.
Section snippets
Connecting obesity and autoimmunity
Obesity corresponds to an abnormal accumulation of adipose tissue within the body. According to World Health Organization (WHO), approximately 35% of the world population is estimated to be overweight (body mass index, BMI 25–30 kg/m2) or obese (BMI > 30 kg/m2) [12]. As mentioned above, it is widely known that obese persons exhibit a subclinical chronic state of inflammation leading to multiple metabolic disorders [13]. Moreover, as will be discussed further below, a large number of studies found a
Leptin
Leptin [33], [34], [35], [36], [37] (from the Greek word leptos = thin) was the first adipokine identified in 1994 by positional cloning of a single gene mutation in the ob/ob mouse. It is a 16 kDa non-glycosylated polypeptide hormone, classified as a member of the long-chain helical cytokine family, such as IL-6, IL-11, IL-12 and Leukemia Inhibitory Factor (LIF). It is encoded by the obese (ob) gene, which is the murine homolog of human Lep gene. Leptin exerts its biological actions through the
Obesity and immune-mediated diseases
An association between obesity and various inflammatory/autoimmune conditions has been suggested in many observational studies. Recently, the discovery of adipokines and better knowledge of their pleiotropic role, particularly on the immune system, has led to major advances in the understanding of the relationships between obesity and autoimmune diseases. Below, we summarize and discuss the data in this field in several immune-mediated conditions. An overview of experimental and clinical data
Conclusion
Currently, many efforts are underway to attempt to explain the recent outbreak of autoimmune diseases, which is a hot topic today. The combination of variety of environmental factors is highly suspected to promote this phenomenon. Of these environmental factors, available data provide strong evidence for the deleterious impact of obesity on several immune-mediated conditions. Thus, obesity clearly appears to increase the risk of developing RA, MS, psoriasis and PsA, and could also promote the
Take-home messages
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White adipose tissue is an active endocrine organ secreting soluble mediators called “adipokines”.
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Adipokines are responsible for a pro-inflammatory state in obese subjects promoting and worsening various pathological conditions.
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Obesity promotes autoimmunity through variety of mechanisms including the secretion of adipokines.
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Obesity may increase the risk of several autoimmune diseases, especially rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, psoriatic arthritis (PsA),
References (364)
- et al.
Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study
Lancet
(Jul 13 2009) - et al.
Infectome: a platform to trace infectious triggers of autoimmunity
Autoimmun Rev
(May 2013) - et al.
Infections, rheumatism and autoimmunity: the conflicting relationship between humans and their environment
Autoimmun Rev
(Oct 2008) - et al.
Infections and autoimmunity—friends or foes?
Trends Immunol
(Aug 2009) - et al.
Geoepidemiology, gender and autoimmune disease
Autoimmun Rev
(May 2012) - et al.
Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells
- et al.
Th17 and regulatory T cell balance in autoimmune and inflammatory diseases
Autoimmun Rev
(Jun 2014) - et al.
Vitamin D and autoimmunity. First part: fundamental aspects
La Rev Méd Interne
(Mar 2012) - et al.
Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence
Autoimmun Rev
(Aug 2013) - et al.
Adipose natural regulatory B cells negatively control adipose tissue inflammation
Adiponectin and interleukin-6 in inflammation-associated disease
Vitam Horm
Diagnosis and classification of rheumatoid arthritis
J Autoimmun
Oral contraceptives, cigarette smoking and other factors in relation to arthritis
Contraception
Adiponectin: a biomarker for rheumatoid arthritis?
Cytokine Growth Factor Rev
Incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001
Open Rheumatol J
Parasitic infection and autoimmunity
Lupus
The mosaic of autoimmunity: the role of environmental factors
Front Biosci (Elite Ed)
Vitamin D in systemic and organ-specific autoimmune diseases
Clin Rev Allergy Immunol
A salty taste to autoimmunity
N Engl J Med
Prevalence and trends in obesity among US adults, 1999–2008
JAMA
Overweight/obesity: overweight by country. Global Health Observatory Data Repository 2008 2013
Adipocytokines in obesity and metabolic disease
J Endocrinol
What's new in our understanding of the role of adipokines in rheumatic diseases?
Obesity is associated with macrophage accumulation in adipose tissue
J Clin Invest
CD8 + effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity
Nat Med
Impacts of the apoptosis inhibitor of macrophage (AIM) on obesity-associated inflammatory diseases
Semin Immunopathol
Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily
J Exp Med
Obesity predisposes to Th17 bias
Eur J Immunol
IL-17 inhibits adipogenesis in part bia C/EBP-alpha, PPAR-gamma and Krüppel-like factors
Cytokine
IL-17 in obesity and adipogenesis
Cytokine Growth Factor Rev
Role of “western diet” in inflammatory autoimmune diseases
Curr Allergy Asthma Rep
Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease
Nutrients
The relationship between vitamin D and obesity
Curr Med Res Opin
The implication of vitamin D and autoimmunity: a comprehensive review
Clin Rev Allergy Immunol
Inflammasome activation in obesity-related inflammatory diseases and autoimmunity
Discov Med
Invariant natural killer T cells in adipose tissue: novel regulators of immune–mediated metabolic disease
Cell Mol Life Sci
Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity
Endocr Regul
Leptin and inflammation
Curr Immunol Rev
The role of adipokines in connective tissue diseases
Eur J Nutr
Obesity, adipose tissue and rheumatoid arthritis: coincidence or more complex relationship?
Clin Exp Rheumatol
Obesity in rheumatoid arthritis
Rheumatology (Oxford)
Adiponectin, an unlocking adipocytokine
Cardiovasc Ther
Elevated adiponectin serum levels in women with systemic autoimmune diseases
Mediators Inflamm
Resistin and Visfatin: regulators of insulin sensitivity inflammation and immunity
Endocr Regul
Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955–2007
Arthritis Rheum
Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden
Ann Rheum Dis
Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation
J Clin Invest
Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis
Arthritis Rheum
Rheumatoid arthritis and cardiovascular disease
Am Heart J
Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment—a position paper of the The Obesity Society and The American Society of Hypertension
Obesity (Silver Spring)
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