Brown adipocyte mineralocorticoid receptor deficiency impairs metabolic regulation in diet-induced obese mice

J Lipid Res. 2023 Sep 19:100449. doi: 10.1016/j.jlr.2023.100449. Online ahead of print.ABSTRACTActivation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high fat diet (HFD) feeding, BAT MR knockout (BMRKO) mice manifested significantly increased body weight, fat mass, serum fasting glucose and impaired glucose homeostasis compared to littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared to LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and pro-inflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced...
Source: Cell Research - Category: Cytology Authors: Source Type: research