Location: Children's Nutrition Research CenterTitle: ApoE and the role of very low density lipoproteins in adipose tissue inflammation Author
Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2012
Publication Date: 6/19/2012
Citation: Wang, J., Perrard, X.D., Mukherjee, A., Rosales, C., Chen, Y., Smith, C.W., Pownall, H.J., Ballantyne, C.M., Wu, H. 2012. ApoE and the role of very low density lipoproteins in adipose tissue inflammation. Atherosclerosis. 223(2):342-349. Interpretive Summary: Apolipoproteins are proteins that carry fat molecules in the blood and deliver them to tissues. To study their possible importance in obesity, mice that were genetically deficient in one of these apolipoproteins were made obese by being fed a high fat diet. The mice deficient in apolipoproteins had less body fat, better glucose responses to insulin, and reduced inflammation in body tissues when compared with normal mice. These studies indicate that apolipoproteins are apparently important in promoting the complications associated with high fat diet-induced obesity.
Technical Abstract: Our goal was too identify the role of triglyceride-rich lipoproteins and apoE, a major apolipoprotein in triglyceride-rich lipoproteins, in adipose tissue inflammation with high-fat diet induced obesity. Male apoE-/- and C57BL/6J wild-type mice fed high fat diets for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE-/- and wild type mice were orally gavaged with [3H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. Very low density lipoproteins from obese apoE-/-mice were intravenously injected into lean wild type or apoE-/- mice to test potential contribution of triglyceride-rich lipoproteins-derived fat delivery to inflammation in adipose tissue and the role of apoE. ApoE-/- mice gained less body weight, and had less fat mass and lower triglyceride levels in skeletal muscle than wild type. ApoE-/- mice on high fat diets had better insulin sensitivity than wild type, even when comparing body weight-matched mice. Compared to wild type mice, apoE-/- mice on high fat diets had lower levels of inflammatory cytokines/chemokines and CD11c in adipose tissue, and lower levels of inflammatory markers in skeletal muscle. At 6 hours after oral gavage with [3H]palmitic acid, incorporation of [3H]palmitic acid into adipose tissue and skeletal muscle was lower in apoE-/- mice. After repeated daily injection for 3 days, VLDL from obese apoE-/- mice induced inflammation in adipose tissue of recipient wild type but not apoE-/- mice. In high fat diet-induced obesity, apoE plays an important role in inflammation in adipose tissue and skeletal muscle, likely by mediating triglyceride-rich lipoproteins-derived fat delivery to these tissues.