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),
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