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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Adipocytes

pathology

Adipose Tissue

chemistry

metabolism

pathology

Animals

Complement C3

deficiency

Complement C3a

analysis

deficiency

Complement Factor B

deficiency

Complement Factor D

deficiency

Complement Pathway

Alternative

genetics

physiology

Diacylglycerol O-Acyltransferase

deficiency

genetics

Fatty Acids

Nonesterified

blood

Female

Leptin

deficiency

Lipoprotein Lipase

genetics

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Mice

Transgenic

Obesity

blood

RNA

Messenger

analysis

Triglycerides

analysis

biosynthesis

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)