title: Variation in the adiponutrin gene influences its expression and associates with obesity.
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.
authors.affiliation: Department of Clinical Sciences Malmö, Clinical Obesity, Lund University, University Hospital MAS, S-205 02 Malmö, Sweden. lovisa.johansson@med.lu.se
authors.forename: Lovisa E
authors.initials: LE
authors.lastname: Johansson
authors.forename: Johan
authors.initials: J
authors.lastname: Hoffstedt
authors.forename: Hemang
authors.initials: H
authors.lastname: Parikh
authors.forename: Emma
authors.initials: E
authors.lastname: Carlsson
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Anne-Greth
authors.initials: AG
authors.lastname: Bondeson
authors.forename: Jan
authors.initials: J
authors.lastname: Hedenbro
authors.forename: Hans
authors.initials: H
authors.lastname: Tornqvist
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Martin
authors.initials: M
authors.lastname: Ridderstråle
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008066:Lipolysis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D007328:Insulin; D008565:Membrane Proteins; D012333:RNA, Messenger; C436316:adiponutrin