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

¹ Institut Cochin, Department of Endocrinology, Cancer and Metabolism, Paris F-75014, France, ² Inserm, U567, Paris F-75014, France, ³ CNRS, UMR 8104, Paris F-75014, France, ⁴ Faculty of Medicine René Descartes, University of Paris 5, UM 3, Paris F-75014, France, ⁵ Laboratory of Metabolic Dysfunction, Department of Nutrition, University of Montréal, Pavillon Liliane de Stewart H3T1A8 Montréal, Québec, Canada, ⁶ INSERM U.449, INRA U.1235, Lyon Centre of Research into Human Nutrition, Faculty of Medicine R. Laennec, University Claude Bernard-Lyon, Lyon, France, ⁷ INSERM, U755 Nutriomique, Paris F-75004, France, ⁸ Faculty of Medicine, University Pierre and Marie Curie-Paris 6, Les Cordeliers, Paris 75004, France, and ⁹ Nutrition Department, AP-HP, Hôtel-Dieu Hospital, Paris 75004, France

(Correspondence should be addressed to K Clément at AP-HP, Hôtel-Dieu Hospital, Paris; Email: karine.clement{at}htd.ap-hop-paris.fr)

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 non-obese 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 (P = 0.008). Its expression was also induced by glucose infusion, although to a lesser extend (2.2-fold, P = 0.03). Infusion of both insulin and glucose (HGHI) had an additive effect on the adiponutrin expression (tenfold, P = 0.008). 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 (P = 0.01), 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.

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				M. Faraj, G. Beauregard, E. Loizon, M. Moldes, K. Clement, Y. Tahiri, K. Cianflone, H. Vidal, and R. Rabasa-Lhoret Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. J. Endocrinol., November 1, 2006; 191(2): 427 - 435. [Abstract] [Full Text] [PDF]