Acylation-stimulating protein deficiency and altered adipose tissue in alternative complement pathway knockout mice

Area of Science:

• Metabolic research
• Adipose tissue biology
• Obesity research

Background:

• Acylation-stimulating protein (ASP) is an adipokine that stimulates triglyceride synthesis in adipose tissue via its receptor C5L2.
• Understanding ASP's role in obesity and its impact on adipose tissue is crucial for metabolic health research.

Purpose of the Study:

• To investigate plasma ASP levels in various mouse models of obesity and leanness.
• To examine the effects of ASP deficiency on adipose tissue morphology and metabolic function in C3 knockout (C3KO) mice.

Main Methods:

• Analysis of plasma ASP levels in wild-type (WT), obese (ob/ob), DGAT1 KO, C/EBPalpha(beta/beta) transgenic, complement factor B knockout (FBKO), and C3 knockout (C3KO) mice.
• Assessment of postprandial triglyceride (TG) and nonesterified fatty acid (NEFA) clearance in FBKO and C3KO mice on low-fat (LF) and high-fat (HF) diets.
• Evaluation of adipocyte size distribution, adipsin expression, DGAT1 expression, and DGAT activity in C3KO mice.

Main Results:

• Plasma ASP levels positively correlated with NEFA and total cholesterol in WT mice.
• ASP levels were significantly increased in obese mice and decreased in lean models.
• ASP deficiency, observed in FBKO and C3KO mice, led to delayed postprandial TG and NEFA clearance, suggesting ASP, not C3, drives this metabolic phenotype.
• C3KO mice exhibited polarized adipocyte size distribution, decreased adipsin and DGAT1 expression, and reduced DGAT activity.

Conclusions:

• Reduced or deficient ASP is linked to an antiadipogenic state.
• ASP plays a significant role in regulating fat metabolism and adipose tissue characteristics.
• ASP represents a potential therapeutic target for managing fat storage and metabolic disorders.