FGF21, energy expenditure and weight loss – How much brown fat do you need?

BACKGROUND: Fibroblast growth factor 21 (FGF21) belongs to the large family of fibroblast growth factors (FGFs). Even though FGF signaling has been mainly implicated in developmental processes, recent studies have demonstrated that FGF21 is an important regulator of whole body energy expenditure and metabolism, in obesity. SCOPE OF REVIEW: Given the fact that obesity has developed epidemic proportions, not just in industrialized countries, FGF21 has emerged as a novel therapeutic avenue to treat obesity as well as associated metabolic disorders. While the metabolic effects of FGF21 are undisputed, the mechanisms by which FGF21 regulate weight loss have not yet been fully resolved. Until recently it was believed that FGF21 induces brown fat activity, thereby enhancing energy expenditure, which concomitantly leads to weight loss. Novel studies have challenged this concept as they could demonstrate that a part of the FGF21 mediated effects are retained in a mouse model of impaired brown adipose tissue function. MAJOR CONCLUSIONS: The review illustrates the recent advances in FGF21 research and discusses the role of FGF21 in the regulation of energy expenditure linked to brown fat activity.