Impact of apolipoprotein A1‐ or Lecithin:cholesterol acyltransferase‐deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

Abstract

High density lipoprotein (HDL) has attracted the attention of the biomedical community due to its well‐documented role in atheroprotection. HDL has been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral tissue insulin sensitivity. Indeed, data from numerous studies strongly indicate that β‐cells, as well as skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet‐induced obesity and type 2 diabetes we aimed at investigating how deficiency in Apoa1 or Lcat, two key proteins of peripheral HDL metabolic pathway, could affect these pathological conditions in mouse models. We report that universal deletion of apoa1 or lcat expression in mice fed western‐type diet results in increased sensitivity to body‐weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discreet effects on WAT metabolic activation and plasma glucose homeostasis. Apoa1‐deficiency results in reduced WAT mitochondrial non‐shivering thermogenesis. Lcat‐deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non‐shivering thermogenesis, rendering lcat−/− mice the most sensitive to weight gain out of the three strains tested, followed by apoa1−/− mice. Nevertheless, only apoa1−/− animals show disturbed plasma glucose homeostasis due to non‐responsive pancreatic β‐islets to glucose and insulin resistant skeletal muscles. Our analyses show that both apoa1−/− and lcat−/− mice fed high‐fat diet have no measurable Apoa1 levels in their plasma, suggesting that other HDL components may be responsible for the observed phenotypic differences among groups.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.