Apelin Enhances Brown Adipogenesis and Browning of White Adipocytes

Aung Than,Si Hui Chua,Melvin Khee-Shing Leow,Lei Sun,Dan Xu,Peng Chen,Hui Ling He

doi:10.1074/jbc.m115.643817

Abstract

Brown adipose tissue expends energy in the form of heat via the mitochondrial uncoupling protein UCP1. Recent studies showed that brown adipose tissue is present in adult humans and may be exploited for its anti-obesity and anti-diabetes actions. Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism. Here, we report that apelin-APJ signaling promotes brown adipocyte differentiation by increasing the expressions of brown adipogenic and thermogenic transcriptional factors via the PI3K/Akt and AMPK signaling pathways. It is also found that apelin relieves the TNFα inhibition on brown adipogenesis. In addition, apelin increases the basal activity of brown adipocytes, as evidenced by the increased PGC1α and UCP1 expressions, mitochondrial biogenesis, and oxygen consumption. Finally, we provide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristics in white adipocytes. This study, for the first time, reveals the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to combat obesity and related metabolic disorders.

Highlights

The autocrine regulatory effects of apelin on self-remodeling of adipose tissue are not known
Apelin-APJ Receptor Promotes Brown Adipocyte Differentiation—Apelin/APJ system is present in Brown adipose tissue (BAT) [39]
Apelin applied at the later stages of differentiation failed to increase the number of brown adipocytes (Fig. 1C), suggesting the importance of apelin signaling in the initiation of brown adipogenesis

Summary

Background

The autocrine regulatory effects of apelin on self-remodeling of adipose tissue are not known. Studies have demonstrated that an increase of beige adipocytes in WAT enhances whole-body energy expenditure and should expectedly reduce the risk of diet-induced obesity and metabolic diseases [14, 15]. It is increasingly recognized that WAT is not merely a passive depot for storage of excess energy as fat and the largest endocrine organ, producing a variety of bioactive factors called adipokines [18] These adipokines play essential roles in regulating energy metabolism and influence adipose tissue’s own remodeling and functions (18 –20). We aim for the first time to reveal the effects of apelin on adipose browning (differentiation of brown preadipocytes in BAT, metabolic activities of mature brown adipocytes, and browning of white adipocytes in WAT)

Experimental Procedures

Results

Discussion