IL-17 — a novel adipose tissue cytokine with anti-adipogenic and pro-osteogenic properties (114.6)

Abstract

Inflammatory mediators have the potential to impact a surprising range of diseases, including obesity, obesity associated metabolic syndrome, and autoimmunity. Adipocyte development and their function in lipid storage and metabolism are regulated in a complex fashion by inflammatory cytokines. Although IL-17 appears to mediate inflammation-associated bone loss, studies indicate IL-17 also has important homeostatic roles in facilitating wound repair and promoting cell proliferation. Recent evidence indicates IL-17 has an anti-adipogenic role while at the same time having an unexpected osteoprotective role; however the mechanisms of IL-17 mediated osteoprotection are ill defined. We show IL-17 is expressed in adipose tissue by leukocytes and is upregulated in obese fat. IL-17 deficiency enhances diet-induced obesity in mice. IL-17 suppresses adipocyte differentiation from mouse derived 3T3-L1 preadipocytes in vitro, and inhibits expression of adipocyte genes. Surprisingly, IL-17R and IL-17 deficiency led to increased bone mineral density in vivo in the absence of inflammation, and IL-17 treatment led to increased osteoblastogenesis in vitro. Over expression of IL-17 inhibited diet-induced obesity while leading to a pro-osteogenic serum profile in mice. Our findings indicate IL-17 as a homeostatic, anti-adipogenic, pro-osteogenic cytokine, capable of inducing osteoblasts from multipotent progenitors, and establishes a potential role for IL-17 in the bone/fat axis.