Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity

Abstract

The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.

Cellular and molecular mechanisms in liver fibrogenesis

“…This adipokine represent the the endogenous ligand of the orphan G protein-coupled receptor APJ, and is known to display a pro-angiogenic role [74]. The interest in apelin, which is expressed and secreted by adipose tissue both in mice and humans [75], has been generated by a study reporting that its levels were markedly increased in cirrhotic liver [76]. Apelin was found to be highly expressed by HSCs and in the same study the use of an antagonist of the apelin receptor was reported to inhibit not only angiogenesis but also hepatic fibrosis.…”

The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice

“…The adipocyte expression of apelin was also found to be increased in rodent models of obesity and reduced in streptozotocin-induced diabetes as well as after fasting, and augmented by insulin, suggesting that insulin is an important regulator of apelin expression (12). Also circulating apelin levels were found to be increased in obesity (12).…”

“…It was recently reported that apelin is expressed in adipocytes (12), which suggests that apelin may function as an adipokine. The adipocyte expression of apelin was also found to be increased in rodent models of obesity and reduced in streptozotocin-induced diabetes as well as after fasting, and augmented by insulin, suggesting that insulin is an important regulator of apelin expression (12).…”

The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

“…Apelin is derived from a larger precursor, preproapelin, the cDNA for which has been cloned in humans, cattle, rats and mice (Tatemoto et al, 1998). Plasma apelin is upregulated in rodents and humans during obesity, there is a strong relationship between adipocyte-secreted apelin and insulin levels (Boucher et al, 2005). In goats, feeding caused a slight increase in plasma apelin concentrations, and this increase was enhanced by water deprivation (Sato et al, 2012).…”