Acylation-stimulating protein deficiency and altered adipose tissue in alternative complement pathway knockout mice.
Acylation-stimulating protein (C3adesArg/ASP) is an adipokine that acts on its receptor C5L2 to stimulate triglyceride (TG) synthesis in adipose tissue. The present study investigated ASP levels in mouse models of obesity and leanness and the effect of ASP deficiency in C3 knockout (C3KO) mice on adipose tissue morphology. Plasma ASP levels in wild-type (WT) mice correlated positively with plasma nonesterified fatty acids (NEFA) (R = 0.664, P < 0.001) and total cholesterol (R = 0.515, P < 0.001). Plasma ASP was increased by 85% in obese ob/ob leptin-deficient mice and decreased in lean diacylglycerol acyltransferase 1 (DGAT1) KO mice (-54%) and C/EBPalpha(beta/beta) transgenic mice (-70%) compared with WT. Mice lacking alternative complement factor B or adipsin (FBKO or ADKO), required for ASP production, were also ASP deficient. Both FBKO and C3KO mice had delayed postprandial TG and NEFA clearance on low-fat (LF) and high-fat (HF) diets, suggesting that lack of ASP, not C3, drives the metabolic phenotype. Adipocyte size distribution in C3KO mice was polarized (increased number of both small and large cells), with decreased adipsin expression (-33% gonadal HF), DGAT1 expression (-31% to -50%) and DGAT activity (-41%). Overall, a reduction/deficiency in ASP is associated with an antiadipogenic state and ASP may provide a target for controlling fat storage.
Paglialunga
Sabina
S
Department of Biochemistry, McGill University, Montreal.
Fisette
Alexandre
A
Yan
Yafeng
Y
Deshaies
Yves
Y
Brouillette
Jean-Francois
JF
Pekna
Marcela
M
Cianflone
Katherine
K
D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003176:Complement C3 / Q000172:deficiency; D015926:Complement C3a / Q000032:analysis / Q000172:deficiency*; D011415:Complement Factor B / Q000172:deficiency; D011416:Complement Factor D / Q000172:deficiency; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000502:physiology*; D051048:Diacylglycerol O-Acyltransferase / Q000172:deficiency / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D020738:Leptin / Q000172:deficiency; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D014280:Triglycerides / Q000032:analysis / Q000096:biosynthesis
D003176:Complement C3; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D012333:RNA, Messenger; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; D008071:Lipoprotein Lipase; D011416:Complement Factor D; D011415:Complement Factor B