Fibroblast growth factor 21 and browning of white adipose tissue

Abstract

Interest has been focused on differentiating anatomical, molecular, and physiological characteristics of the types of mammalian adipose tissues. White adipose tissue (WAT) and brown adipose tissue (BAT) are the two main forms of adipose tissue in humans. WAT functions as an endocrine organ and serves as a reservoir of energy in the form of triglycerides. The hormones released by WAT are called adipokines. BAT consists of a group of specialized cells with abundant uncoupling protein 1 (UCP1) in the inner mitochondrial membrane and also fulfills endocrine functions. Following the identification of functional (BAT) in human adults, there has been a great deal of interest in finding out how it is induced, its localization, and the mechanisms by which it regulates thermogenesis. Fibroblast growth factor 21 (FGF21) is a key regulator of the differentiation to brown adipocytes. The main mechanisms occur through enhancing UCP1 expression. In addition, following exposure to cold or exercise, FGF21 induces upregulation of local peroxisome proliferator-activated receptor gamma co-activator (PGC)-1-alfa and thus promotes thermogenesis in adipose tissue and skeletal muscle. FGF21 integrates several pathways allowing the regulation of human energy balance, glucose levels, and lipid metabolism. Such mechanisms and their clinical relevance are summarized in this review.