Adiponutrin gene is regulated by insulin and glucose in human adipose tissue

Abstract

Objective: Adiponutrin is a new transmembrane protein specifically expressed in adipose tissue. In obese subjects, short-or long-term calorie restriction diets were associated with a reduction in adiponutrin gene expression. Adiponut.rin mRNA level was previously shown to be negatively correlated with fasting glucose plasma levels and associated with insulin sensitivity of non-diabetic obese and nonobese subjects. The purpose of the present work was to get more insight into the regulation of adiponutrin gene expression by insulin and/or glucose using clamp studies and to examine its potential dysregulation in subjects with a deterioration of glucose homeostasis. Methods: Adiponutrin gene expression was quantified by reverse transcriptase-quantitative PCR in s.c. adipose tissue of healthy lean subjects after an euglycemic hyperinsulinemic clamp (EGHI), a hyperglycemic euinsulinemic clamp, and a hyperglycemic hyperinsulinemic (HGHI) clamp. Adiponutrin gene expression was also analyzed in patients with different levels of insulin resistance. Results: During EGHI, insulin infusion induced adiponutrin gene expression 8.4-fold (PZ0.008). Its expression was also induced by glucose infusion, although to a lesser extend (2.2-fold, PZ0.03). Infusion of both insulin and glucose (HGHI) had an additive effect on the adiponutrin expression (tenfold, PZ0.008). In a pathological context, adiponutrin gene was highly expressed in the adipose tissue of type-1 diabetic patients with chronic hyperglycemia compared with healthy subjects. Conversely, adiponutrin gene expression was significantly reduced in type-2 diabetics (PZ0.01), but remained moderately regulated in these patients after the EGHI clamp (2.5-fold increased). Conclusion: These results suggest a strong relationship between adiponutrin expression, insulin sensitivity, and glucose metabolism in human adipose tissue. European Journal of Endocrinology 155 461-468

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

“…Recent findings by our group and others indicate that, despite being a WAT-derived protein, adiponutrin expression is not elevated in obese subjects (Liu et al 2004, Moldes et al 2006. Furthermore, fasting adiponutrin expression as well as insulin-stimulated increase in adiponutrin expression were reduced in obese type 2 diabetic subjects when compared with controls (Moldes et al 2006).…”

“…Furthermore, fasting adiponutrin expression as well as insulin-stimulated increase in adiponutrin expression were reduced in obese type 2 diabetic subjects when compared with controls (Moldes et al 2006). Therefore, the regulation of adiponutrin expression in human may be altered by reduced insulin sensitivity and altered regulation of WATderived proteins in relation to insulin signaling and action in states like type 2 diabetes.…”

“…Recently, we examined the regulation of adiponutrin expression by hyperinsulinemia in type 2 diabetic obese subjects. Despite their obese state and the origin of adiponutrin being WAT, fasting adiponutrin expression as well as insulinstimulated increase in adiponutrin expression were reduced in obese diabetic subjects when compared with controls (Moldes et al 2006).…”

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

“…Although its putative role in metabolic disease development has only recently started to be explored, various genome-wide association studies have identified the Pnpla3 gene to be associated with liver-related phenotypes (Romeo et al 2008, Yuan et al 2008, Kotronen et al 2009). Since it is up-regulated in response to feeding and downregulated in the fasted state, a potential role for Pnpla3 in lipid storage has been suggested (Baulande et al 2001, Lake et al 2005, Moldes et al 2006, Wilson et al 2006. Furthermore, the transcription factors SREBPs, PPARg and ChREBP have been shown to mediate increased expression of the Pnpla3 gene (Baulande et al 2001, Polson & Thompson 2003.…”

Les protéines à domaine patatine

“…Indétectable à jeun, elle est très fortement augmentée après une prise alimentaire [31]. L'insuline et le glucose induisent l'expression de l'adiponutrine [32] qui est surexprimée dans des modèles murins d'obésité [31] ainsi que chez des patients obèses ou insulinorésistants [32]. La protéine est localisée au niveau des structures membranaires du cytoplasme comme l'appareil de Golgi ou le réticulum endoplasmique, site principal de synthèse des lipides dans les cellules de mammifères [31].…”