Adiponectin gene expression is inhibited by β‐adrenergic stimulation via protein kinase A in 3T3‐L1 adipocytes

Abstract

Recently, it has been shown that the fat-derived factor adiponectin is downregulated in insulin resistance and obesity and that replenishment of this adipocytokine reverses insulin resistance in mice. Growing evidence, on the other hand, suggests that raised levels of catecholamines due to increased activity of the sympathetic nervous system are an integral part in the development of insulin resistance. To clarify whether catecholamines might exert their insulin resistance-inducing effects at least partly via downregulation of adiponectin gene expression, 3T3-L1 adipocytes were treated with isoproterenol, and adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. In fact, isoproterenol treatment reduced the level of adiponectin mRNA by about 75% in a dose-dependent fashion with significant inhibition detectable at concentrations as low as 10 nM isoproterenol. Furthermore, the inhibitory effect of isoproterenol was almost completely reversed by pretreatment of 3T3-L1 cells with the L L-adrenergic antagonist propranolol and the protein kinase A (PKA) inhibitor H-89. Moreover, the effects of isoproterenol could be mimicked by stimulation of stimulatory guanine nucleotide-binding (G S )-proteins with cholera toxin and adenylyl cyclase with forskolin. Thus, our results suggest that adiponectin gene expression is severely suppressed by L L-adrenergic agents via activation of a G S -protein^PKA-dependent pathway. The data support a possible role of adiponectin in catecholamine-induced insulin resistance. ß

The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass

“…Interestingly, a recent paper [33] shows a significant negative relationship between a sympathetic predominance at the heart level and circulating adiponectin levels. Adiponectin secretion is submitted to an inhibitory control by the adrenergic system [34]. This result, therefore, suggests that an increased sympathetic cardiac activity parallels a sympathetic predominance in the adipose tissue.…”

Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

“…Some other studies have reported similar disassociation between adiponectin levels and insulin resistance 28,29 and the relationship between adiponectin and IR is probably not one of the direct cause and effect in all patients. It is possible that their inverse relationship may be mediated not only by insulin levels but also by other hormones such as catecholamines or androgens, [30][31][32] as well as by pro-inflammatory cytokines, 33,34 and some medications. 31,35 Our results also depict the prominent role that adipose tissue plays in both insulin resistance and the clinical expression of the metabolic syndrome (Figures 1 and 2).…”

Regulation of adipocytokines and insulin resistance

“…Various hormones inducing insulin resistance down-regulate adiponectin expression. Thus, β-adrenergic activation inhibits adiponectin mRNA expression by up to 75% in differentiated 3T3-L1 cells in vitro (Table 1) [97]. Similarly, adiponectin mRNA and protein synthesis are down-regulated in human adipocytes in vitro by β-adrenoceptor agonists with β3-agonists having the most potent effects [98].…”