Increased Adipocyte S-Nitrosylation Targets Anti-lipolytic Action of Insulin

• DOI: 10.1074/jbc.m111.235945
• Publication Date: 2011-07-04T02:00:25Z
• Authors: Hilla Ovadia; Yulia Haim; Ori Nov; Orna Almog; Julia Kovsan; Nava Bashan; Moran Benhar; Assaf Rudich
• Keywords: S-Nitrosylation

Protein S-nitrosylation is a reversible protein modification implicated in both physiological and pathophysiological regulation of function. In obesity, skeletal muscle insulin resistance associated with increased insulin-signaling proteins. However, whether adipose tissue similarly affected obesity and, if so, what are the causes functional consequences this unknown. Total was intra-abdominal obese humans high fat-fed or leptin-deficient ob/ob mice. Both receptor β-subunit Akt were S-nitrosylated, correlating body weight. Elevated mRNA expression inducible NO synthase decreased levels thioredoxin reductase S-nitrosylation. Cultured differentiated pre-adipocyte cell lines exposed to donors S-nitrosoglutathione (GSNO) S-nitroso-N-acetylpenicillamine exhibited diminished insulin-stimulated phosphorylation but not GSK3 nor glucose uptake. Yet anti-lipolytic action markedly impaired cultured adipocytes mice injected GSNO prior administration insulin. cells, ability diminish phosphorylated PKA substrates response isoproterenol suggested insulin-induced activation PDE3B. Consistently, PDE3B detected Site-directed mutagenesis revealed that Cys-768 Cys-1040, two putative sites for adjacent substrate-binding site PDE3B, accounted ∼50% its GSNO-induced Collectively, may constitute novel targets obesity.