Adipokines in Healthy Skeletal Muscle and Metabolic Disease

Abstract

Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross-talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease.

Interactions of exercise training and high-fat diet on adiponectin forms and muscle receptors in mice

“…In this study, mice exposed to 10 weeks of an HF diet recapitulated the key problems of MetS [28]: an increased caloric intake, reflecting reduced satiety control, as well as increased body weight and fat mass associated with impaired glucose tolerance. Paradoxically, these disturbances were associated to an increased plasmatic leptin level, a hormone reducing food intake and increasing energy expenditure, insulin sensitivity and fat deposition [29]. These results could be explained by a leptin resistance, preventing its central and peripheral functions [30].…”

Ethanol extracts of <i>Aster yomena</i> (Kitam.) Honda inhibit adipogenesis through the activation of the AMPK signaling pathway in 3T3-L1 preadipocytes

“…In addition, AMPK activation by phosphorylation can reduce the degree of obesity by inhibiting adipocyte differentiation by changing the expression and activity of the enzymes and proteins involved in lipid metabolism (16,19). Furthermore, ACC, a downstream substrate of AMPK, is a rate-limiting enzyme that limits the critical rates in fatty acid synthesis and oxidation, reducing the fatty acid and lipid synthesis to inhibit the onset and progression of obesity (13,18). Therefore, AMPK signaling has gained the attention of researchers as a molecular target for fighting obesity.…”

“…The activation of AMKP inhibits preadipocyte differentiation and adipogenesis through increased phosphorylation of ACC, a substrate of AMPK (13,17). To investigate whether AMPK is activated by EEAY during 3T3-L1 differentiation, we analyzed the levels of phosphorylated AMPK and ACC and found that EEAY remarkably enhanced the phosphorylation of AMPK and ACC without altering the expression of their total protein expression, indicating the activation of the AMPK pathway.…”

“…In the final stages of the differentiation, adipocytes secrete adipose tissue-specific products, including adipocyte-specific fatty acid binding protein (aP2) and leptin (8)(9)(10)(11). After differentiation, they regulate the lipid metabolism by synthesizing lipolytic enzymes such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and hormone-sensitive lipase (12,13). Therefore, the inhibition of the differentiation of preadipocytes into adipocytes would reduce the mass of adipose tissue and reduce the incidence of obesity.…”

“…The activated AMPK increases glucose transport and fatty acid oxidation; it also inhibits the energy-consuming processes such as lipogenesis, protein synthesis, and gluconeogenesis (18,19). AMPK also induces inactivation by phosphorylating ACC, the key enzyme for fatty acid oxidation and biosynthesis (13,20). Further, when AMKP is activated, it may protect preadipocyte differentiation with the inhibition of the transcription factors such as PPARγ and C/EBPs.…”