Interleukin-6: An Under-Appreciated Inducer of Thermogenic Adipocyte Differentiation

Adipose tissue inflammation is a key factor leading to obesity-associated immune disorders, such as insulin resistance, beta cell loss in the pancreatic islets, meta-inflammation, and autoimmunity. Inhibiting adipose tissue inflammation is considered a straightforward approach to abrogate these diseases. However, recent findings show that certain pro-inflammatory cytokines are essential for the proper differentiation and functioning of adipocytes. Lipolysis is stimulated, and the thermogenic competence of adipocytes is unlocked by interleukin-6 (IL-6), a cytokine that was initially recognized as a key trigger of adipose tissue inflammation. Coherently, signal transducer and activator of transcription 3 (STAT3), which is a signal transducer for IL-6, is necessary for thermogenic adipocyte development. Given the impact of thermogenic adipocytes in increasing energy expenditure and reducing body adiposity, functions of IL-6 in the adipose tissue have gained attention recently. In this review, we show that IL-6 signaling may protect from excess fat accumulation by stimulating thermogenesis in adipocytes.