期刊
JOURNAL OF LIPID RESEARCH
卷 56, 期 3, 页码 526-536出版社
ELSEVIER
DOI: 10.1194/jlr.M054080
关键词
diacylglycerol; dyslipidemias; insulin signaling; lipase/lipoprotein; apolipoprotein; protein kinase C; lipid uptake; insulin resistance; nonalcoholic fatty liver disease
资金
- National Institutes of Health [R01 DK-40936, R24 DK-085638, U24 DK-059635, P30 DK-45735, R01 NS-087568, R01-AG-23686]
- ADA-Distinguished Clinical Investigator Award
- ADA-Merck Mentor Based Clinical/Translational Science Post-doctoral Fellowship Award from the American Diabetes Association [1-14-10 Merck]
- Novo Nordisk Foundation Center for Basic Metabolic Research
ApoA5 has a critical role in the regulation of plasma TG concentrations. In order to determine whether ApoA5 also impacts ectopic lipid deposition in liver and skeletal muscle, as well as tissue insulin sensitivity, we treated mice with an antisense oligonucleotide (ASO) to decrease hepatic expression of ApoA5. ASO treatment reduced ApoA5 protein expression in liver by 60-70%. ApoA5 ASO-treated mice displayed approximately 3-fold higher plasma TG concentrations, which were associated with decreased plasma TG clearance. Furthermore, ApoA5 ASO-treated mice fed a high-fat diet (HFD) exhibited reduced liver and skeletal muscle TG uptake and reduced liver and muscle TG and diacylglycerol (DAG) content. HFD-fed ApoA5 ASO-treated mice were protected from HFD-induced insulin resistance, as assessed by hyperinsulinemic-euglycemic clamps. This protection could be attributed to increases in both hepatic and peripheral insulin responsiveness associated with decreased DAG activation of protein kinase C (PKC)-epsilon and PKC theta in liver and muscle, respectively, and increased insulin-stimulated AKT2 phosphory lation in these tissues. In summary, these studies demonstrate a novel role for ApoA5 as a modulator of susceptibility to diet-induced liver and muscle insulin resistance through regulation of ectopic lipid accumulation in liver and skeletal muscle.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据