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Diabetes Publish Ahead of Print published online ahead of print March 28, 2008
DOI: 10.2337/db07-0435
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Original Research

Adiponectin Reduces Plasma Triglyceride by Increasing VLDL-Triglyceride Catabolism

Liping Qiao, MD1, Chenhui Zou, Ph.D.1, Deneys R. van der Westhuyzen, Ph.D.1,,2, and Jianhua Shao, M.D., Ph.D.1

1Graduate Center for Nutritional Sciences
2Department of Internal Medicine and Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky 40536, USA

Objective: Adiponectin is an adipocyte-derived hormone that plays an important role in glucose and lipid metabolism. The main aims of this study are to investigate the effects of adiponectin on very low density lipoprotein triglyceride (VLDL-TG) metabolism and the underlying mechanism.

Research Design and Methods: Adenoviruses were used to generate a mouse model with elevated circulating adiponectin. HepG2 and C2C12 cells were treated with recombinant human adiponectin.

Results: Three days after Ad-mACRP30 adenovirus injection, plasma adiponectin protein levels were increased 12-fold. All three main multimeric adiponectin molecules were proportionally elevated. Fasting plasma triglyceride levels were significant decreased (~40%) in the mice with elevated adiponectin in circulation, as were the plasma levels of large and medium-sized VLDL subclasses. Although apolipoprotein B mRNA levels were robustly suppressed in the livers of adiponectin overexpressing mice and in cultured HepG2 cells treated with recombinant human adiponectin, hepatic VLDL-TG secretion rates were not altered by elevated plasma adiponectin. However, Ad-mACRP30-treated mice exhibited a significant increase of post-heparin plasma lipoprotein lipase (LPL) activity compared with mice that received control viral vector. Skeletal muscle LPL activity and mRNA levels of LPL and VLDL receptor were also increased in Ad-mACRP30 treated mice. Recombinant human adiponectin treatment increased LPL and VLDL receptor mRNA levels in differentiated C1C12 myotubes.

Conclusions: These results suggest that adiponectin decreases plasma triglyceride levels by increasing skeletal muscle LPL and VLDL receptor expression and consequently VLDL-TG catabolism.

Correspondence: JianhuaShao{at}uky.edu

Key Words: adiponectin • triglyceride • muscle • lipoprotein • obesity


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