title: Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion.
abstract: BACKGROUND
  Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca(2+)-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level.
  
  
  RESULTS
  We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER) was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3) in skeletal muscle was approximately doubled in the KO mice compared with control mice.
  
  
  CONCLUSIONS
  These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model.
authors: Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore.
authors: Phing-How
authors: PH
authors: Lou
authors: Natalia
authors: N
authors: Gustavsson
authors: Yue
authors: Y
authors: Wang
authors: George K
authors: GK
authors: Radda
authors: Weiping
authors: W
authors: Han
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050356:Lipid Metabolism; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D050857:Synaptotagmins / Q000172:deficiency*
chemical_list: D005227:Fatty Acids; D007328:Insulin; D050857:Synaptotagmins; D005934:Glucagon