Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance—notably through cytokine and chemokine secretion—and highlights major research questions in the field. 1. Adipose Tissue Inflammation Is Crucial in the Development of Obesity-Induced Insulin Resistance Obesity is a growing epidemic worldwide; its prevalence has been rising tremendously over the last 30 years (WHO, 2013). Excess adiposity is an established risk factor for metabolic diseases including insulin resistance, type 2 diabetes (T2D), hypertension, nonalcoholic fatty liver disease (NAFLD), polycystic ovarian diseases, and several types of cancer [1]. Obesity is a proinflammatory condition in which hypertrophied adipocytes and adipose tissue-resident immune cells (primarily lymphocytes and macrophages) both contribute to increased circulating levels of proinflammatory cytokines. The obesity-associated state of chronic low-grade systemic inflammation, termed “metabolic inflammation,” is considered a focal point in the pathogenesis of insulin resistance and T2D in humans and rodent animal models [2–5]. Although liver and muscle show obesity-induced mild inflammatory responses, white adipose tissue (WAT) is the key site mediating systemic inflammation [6]. 1.1. Adipose Tissue Promotes an Inflammatory Response in Obesity: Role of TNF-α, IL-6, Leptin, Adiponectin, and Resistin in Insulin Resistance Adipose tissue primary function is to store excess nutrients as triacylglycerols and to release free fatty acids during fasting. A major step forward to the
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