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Adipocyte‐specific Loss of Retinoic Acid Receptor Alpha (Rarα) Exacerbates Diet‐induced Obesity and Steatohepatitis in Mice
Author(s) -
Cassim Bawa Fathima,
Xu Yanyong,
Gopoju Raja,
Hu Shuwei,
Zhu Yingdong,
Chen Shaoru,
Jadhav Kavita,
Zhang Yanqiao
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05330
Subject(s) - endocrinology , medicine , adipocyte , adiponectin , adipogenesis , adipose tissue , retinoic acid receptor , steatosis , lipid metabolism , white adipose tissue , insulin resistance , steatohepatitis , adipokine , biology , triglyceride , retinoic acid , chemistry , fatty liver , insulin , biochemistry , cholesterol , disease , gene
Adipocytes are the major sites of lipid storage and important for regulating lipid metabolism. Adipocytes also serve as the adipokine‐releasing cells that mediates lipid and glucose homeostasis in the body. Under diet‐induced conditions impaired lipid metabolism in adipocytes can lead to ectopic lipid accumulation and insulin resistance. Previous studies show that activation of retinoic acid receptors via retinoic acid signaling can inhibit adipogenesis and promote adipose tissue browning. We hypothesized that adipocyte‐specific retinoic acid receptor alpha (Rarα) might play a role in protecting against diet‐induced obesity. To test this hypothesis, we conducted in‐vivo studies using adipocyte‐specific Rarα knockout mice. Rarα floxed mice were crossed with adiponectin‐Cre transgenic mice to generate adipocyte‐specific knockout mice (adipo‐Rarα ‐/‐ ). Rarα fl/fl (control) and adipo‐Rarα ‐/‐ mice were given a high fat diet for 20 weeks. During the study, the body weight of adipo‐Rarα ‐/‐ significantly increased compared to control. The body composition analysis showed that loss of Rarα in adipocytes increased body fat content. Indirect calorimetry studies showed that reduced energy expenditure in adipo‐Rarα ‐/‐ mice. Histological analysis showed that brown adipose tissue had increased lipid deposition. Adipo‐Rarα ‐/‐ mice also had impaired glucose tolerance. In the liver, adipo‐Rarα ‐/‐ mice had increased triglyceride and non‐esterified free fatty acid accumulation, and fibrosis. In the plasma, adipo‐Rarα ‐/‐ mice and increased free fatty acid, AST and ALT levels. Thus, our study indicates that adipocyte RARα is protective against obesity and steatohepatitis.