title: Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice.
abstract: Acylation-stimulating protein (ASP) acts as a paracrine signal to increase triglyceride synthesis in adipocytes. ASP administration results in more rapid postprandial lipid clearance. In mice, C3 (the precursor to ASP) knockout results in ASP deficiency and leads to reduced body fat and leptin levels. The protective potential of ASP deficiency against obesity and involvement of the leptin pathway were examined in ob/ob C3(-/-) double knockout mice (2KO). Compared with age-matched ob/ob mice, 2KO mice had delayed postprandial triglyceride and fatty acid clearance; associated with decreased body weight (4-17 weeks age: male: -13.7%, female: -20.6%, p < 0.0001) and HOMA (homeostasis model assessment) index (-37.7%), suggesting increased insulin sensitivity. By contrast, food intake in 2KO mice was +9.1% higher over ob/ob mice (p < 0.001, 2KO 5.1 +/- 0.2 g/day, ob/ob 4.5 +/- 0.2 g/day, wild type 2.6 +/- 0.1 g/day). The hyperphagia/leanness was balanced by a 28.5% increase in energy expenditure (oxygen consumption: 2KO, 131 +/- 8.9 ml/h; ob/ob, 102 +/- 4.5 ml/h; p < 0.01; wild type, 144 +/- 8.9 ml/h). These results suggest that the ASP regulation of energy storage may influence energy expenditure and dynamic metabolic balance.
authors.affiliation: Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Center, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Zhunan
authors.initials: Z
authors.lastname: Xia
authors.forename: Allan D
authors.initials: AD
authors.lastname: Sniderman
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000502:physiology*; D015926:Complement C3a / Q000031:analogs & derivatives*; D017931:DNA Primers; D004734:Energy Metabolism; D005260:Female; D020738:Leptin / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*
chemical_list: D001798:Blood Proteins; D017931:DNA Primers; D020738:Leptin; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a