Variation in the adiponutrin gene influences its expression and associates with obesity.
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.
Johansson
Lovisa E
LE
Department of Clinical Sciences Malmö, Clinical Obesity, Lund University, University Hospital MAS, S-205 02 Malmö, Sweden. lovisa.johansson@med.lu.se
Hoffstedt
Johan
J
Parikh
Hemang
H
Carlsson
Emma
E
Wabitsch
Martin
M
Bondeson
Anne-Greth
AG
Hedenbro
Jan
J
Tornqvist
Hans
H
Groop
Leif
L
Ridderstråle
Martin
M
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
D007328:Insulin; D008565:Membrane Proteins; D012333:RNA, Messenger; C436316:adiponutrin