IL-17 in obesity and adipogenesis

Abstract

The pro-inflammatory cytokine interleukin (IL)-17 (also known as IL-17) has been associated with induction of tissue inflammation. Obese individuals exhibit many symptoms of chronic low-grade inflammation, suggesting that IL-17 may impact adipose tissue. However, the role of IL-17 in obesity is largely unexplored. Emerging studies indicate that obesity selectively promotes expansion of the Th17 T-cell lineage, exacerbating disease in murine models of autoimmunity such as EAE and colitis. Human studies support this concept, as new clinical studies suggest that IL-17 is expressed at elevated levels in obese individuals. Conversely, however, an anti-adipogenic role for IL-17 is becoming evident, and therefore the interconnections between IL-17 and fat metabolism may be quite complex. Here, we consolidate the potential implications of IL-17 in relation to obesity and describe the emerging data regarding the role of IL-17 in adipose tissue.

Figure 1. Effects of IL-17A during acute inflammation associated with obesity

(A) T-cells from diet-induced obese (DIO) mice expand Th17 cell pools and produce progressively more IL-17 than lean littermates, in what has been shown to be an IL-6-dependent process. The increased Th17 bias is associated with more pronounced autoimmune disease during EAE and trinitrobenzene sulfonic acid colitis. In both models DIO mice developed more severe early autoimmune disease, with increased pools of IL-17⁺ T-cells (26). (B) Levels of IL-17A in peritoneal fluid in response to ZY are elevated in obese leptin-deficient ob/ob mice compared with lean animals. IL-17A is increased in obese mice during acute inflammation and contributes to exacerbation of inflammatory responses, but the cellular sources of IL-17A remain controversial (34).

Figure 2. Model for inhibition differentiation of adipocytes by IL-17A

IL-17A promotes mesenchymal stem cells to undergo osteoblastogenesis and inhibit adipogenesis (39, 43). IL-17A exhibits the inhibitory effect on adipogenesis in part by the secretion of PGE₂ via COX-2 induction in differentiated adipocytes (42). During the inhibition of adipogenesis it is not clear whether IL-17RA signaling involves C/EBPβ or other transcription factors. It is also unclear whether the IL-17A-induced expression of IL-6 from adipose tissue under conditions of obesity affects differentiation of naïve T lymphocytes into Th17 cells.