High-Density Lipoprotein Metabolism in Human Apolipoprotein B₁₀₀ Transgenic/Brown Adipose Tissue Deficient Mice: A Model of Obesity-Induced Hyperinsulinemia

Authors

Sarah J. Ehlers, University of Nebraska-Lincoln
Stephanie M. Larson, University of Nebraska-Lincoln
Heather E. Rasmussen, University of Nebraska-LincolnFollow
Young-Ki Park, University of Nebraska-LincolnFollow
Ji-Young Lee, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

6-2011

Citation

Applied Physiology, Nutrition, and Metabolism 36:3 (June 2011), pp. 313–322.

doi: 10.1139/H11-003

Comments

Copyright © 2011 Sarah J. Ehlers, Stephanie M. Larson, Heather E. Rasmussen, Young-Ki Park, and Ji-Young Lee; published by NRC Research Press. Used by permission.

Abstract

Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B₁₀₀ transgenic (hApoB^tg) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoB^tg/BATless mice. Male and female hApoB^tg and hApoB^tg/BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoB^tg/BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoB^tg counterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoB^tg/BATless mice with no difference in mRNA levels compared with hApoB^tg counterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoB^tg/BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesity-induced hyperinsulinemia.