Acylation-stimulating protein (ASP)/complement C3adesArg deficiency results in increased energy expenditure in mice.
Acylation-stimulating protein (ASP) acts as a paracrine signal to increase triglyceride synthesis in adipocytes. In mice, C3 (the precursor to ASP) knock-out (KO) results in ASP deficiency and leads to reduced body fat and leptin levels yet they are hyperphagic. In the present study, we investigated the mechanism for this energy repartitioning. Compared with wild-type (WT) mice, male and female C3(-/-) ASP-deficient mice had elevated oxygen consumption (VO2) in both the active (dark) and resting (light) phases of the diurnal cycle: +8.9% males (p < 0.05) +9.4% females (p < 0.05). Increased physical activity (movement) was observed during the dark phase in female but not in male KO animals. Female WT mice moved 16.9 +/- 2.4 m whereas KO mice moved 30.1 +/- 5.4 m, over 12 h, +78.4%, p < 0.05). In contrast, there was no difference in physical activity in male mice, but a repartitioning of dietary fat following intragastric fat administration was noted. This was reflected by increased fatty acid oxidation in liver and muscle in KO mice, with increased UCP2 (inguinal fat) and UCP3 (muscle) mRNA expression (p = 0.005 and 0.036, respectively). Fatty acid uptake into brown adipose tissue (BAT) and white adipose tissue (WAT) was reduced as reflected by a decrease in the fatty acid incorporation into lipids (BAT -68%, WAT -29%. The decrease of FA incorporation was normalized by intraperitoneal administration of ASP at the time of oral fat administration. These results suggest that ASP deficiency results in energy repartitioning through different mechanisms in male and female mice.
Xia
Zhunan
Z
Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal H3A 1A1, Canada.
Stanhope
Kimber L
KL
Digitale
Erin
E
Simion
Oana-Maria
OM
Chen
Lanying
L
Havel
Peter
P
Cianflone
Katherine
K
D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000172:deficiency* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007473:Ion Channels; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D001798:Blood Proteins; D002352:Carrier Proteins; D004041:Dietary Fats; D005227:Fatty Acids; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a