Variation in the Adiponutrin Gene Influences Its Expression and Associates With Obesity
- Lovisa E. Johansson1,
- Johan Hoffstedt2,
- Hemang Parikh3,
- Emma Carlsson1,
- Martin Wabitsch4,
- Anne-Greth Bondeson5,
- Jan Hedenbro6,
- Hans Tornqvist17,
- Leif Groop3 and
- Martin Ridderstråle1
- 1Department of Clinical Sciences Malmö, Clinical Obesity, Lund University, University Hospital MAS, Malmö, Sweden
- 2Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden
- 3Department of Clinical Sciences Malmö, Diabetes and Endocrinology, Lund University, University Hospital MAS, Malmö, Sweden
- 4Department of Pediatrics, University of Ulm, Ulm, Germany
- 5Department of Clinical Sciences Malmö, Emergency Medicine/Medicine/Surgery, Lund University, University Hospital MAS, Malmö, Sweden
- 6Department of Clinical Sciences Lund, Lund University, Lund University Hospital, Lund, Sweden
- 7Department of Diabetes Biology, Novo Nordisk, Målöv, Denmark
- Address correspondence and reprint requests to Lovisa E. Johansson, Department of Clinical Sciences Malmö, Clinical Obesity, Lund University, Wallenberg Laboratory, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail: lovisa.johansson{at}med.lu.se
Abstract
Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is downregulated by fasting and upregulated by refeeding, suggesting a role in lipogenesis. Experiments in human adipocytes confirmed that the gene is upregulated in response to insulin in a glucose-dependent fashion. Obese subjects had increased levels of subcutaneous and visceral abdominal adipose tissue ADPN mRNA. Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment). We also studied genetic variation in ADPN and its relation to obesity, lipolysis, and mRNA expression. Two ADPN polymorphisms showed association with obesity. Carriers of the obesity-associated variants showed a lesser increase in the levels of adipose tissue ADPN mRNA and an increased basal lipolysis. Our results suggest that obese subjects that are insulin resistant and/or carriers of the obesity-associated ADPN alleles fail to upregulate the gene and that upregulation of adiponutrin may be an appropriate response to orchestrate energy excess.
- HOMA, homeostasis model assessment
- HSL, hormone-sensitive lipase
- iPLA2, identical to calcium-independent phospholipase A2
- SNP, single nucleotide polymorphism
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
L.G. has been a paid consultant for and has served on advisory boards for Aventis-Sanofi, Bristol-Myers Squibb, Kowa, and Roche.
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
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- Accepted November 23, 2005.
- Received August 19, 2005.
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