Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin

Abstract

Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulinstimulated states. To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85a PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). At baseline (NZ20), adiponutrin expressions were positively correlated with those of p85a PI3K (RZ0 . 54 levels. In healthy young men, adiponutrin expression is unregulated by hyperinsulinemia and is related to basal and/or insulin-stimulated p85a PI3K, HKII, adiponectin, and leptin expression levels. We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. The relevance of the present findings to reduced adiponutrin expression in type 2 diabetes is discussed.

Investigation of PNPLA3 and IL28B Genotypes on Diabetes and Obesity After Liver Transplantation: Insight Into Mechanisms of Disease

“…However, the frequency of GG polymorphism is close to twice the normal population (which is $5%) (19,25), possibly relating to the increased risk of liver disease progression, resulting in a GG enriched population. Although some studies have suggested less of an association of PNPLA-3 polymorphisms with insulin resistance or obesity (14,18,19,26), mechanistic studies have linked glucose metabolism and obesity with PNPLA-3 stimulation and protein production in the insulin sensitive individual (24,27,28). This study extends the link between PNPLA-3 gene polymorphisms and obesity.…”

Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity

“…Insulin regulates the gene positively in a glucose-dependent fashion. As a consequence of the elevated fasting insulin levels associated with obesity, PNPLA3 mRNA was increased in obese compared with lean human subjects in our previous study (6) where it otherwise would be greatly reduced in the fasting state (7)(8)(9). Subjects that are insulin resistant have a lesser increase of adipose tissue PNPLA3 mRNA expression despite elevated insulin levels (6).…”

“…Adipose tissue PNPLA3 mRNA expression is influenced by nutritional status, insulin and insulin sensitivity, degree of obesity, and genetic variants in the PNPLA3 gene (3,4,(6)(7)(8)(9)(17)(18)(19). The knowledge regarding the role of adiponutrin in the adipocyte or any other cell is still very limited, making it difficult to functionally understand a link between adiponutrin and insulin secretion.…”

Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome

“…Like Pnpla2/ATGL , Pnpla3 expression is altered in obesity-related dysmetabolic states ( 12,25,(27)(28)(29). Also like Pnpla2/ATGL , Pnpla3 expression is strongly regulated by a variety of important nutritional (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), hormonal ( 25,27,35,(39)(40)(41), and pharmacological factors ( 36,38,42 ), although Pnpla2 and Pnpla3 are usually regulated in the opposite direction from each other. The regulation and subcellular localization of PNPLA3 are most consistent with a role in anabolic lipid metabolism (i.e., lipogenesis).…”