Open AccessADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice
Author(s) -
Xiaobing Cui,
Fu Jia,
Sisi Chen,
Gaylen L. Edwards,
Shiyou Chen
Publication year - 2021
Publication title -
endocrinology and metabolism/american journal of physiology: endocrinology and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.507
H-Index - 201
eISSN - 1522-1555
pISSN - 0193-1849
DOI - 10.1152/ajpendo.00175.2020
Subject(s) - ghrelin , endocrinology , medicine , appetite , insulin resistance , adenosine deaminase , obesity , biology , adenosine , hormone
Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient ( Adar1 +/- ) mice were fed normal chow or a high-fat diet (HFD) for 12 wk. Adar1 +/- mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1 +/- improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1 +/- mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1 +/- protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1 +/- restored the increased ghrelin expression in the stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induced obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion. NEW & NOTEWORTHY This study identifies adenosine deaminase acting on RNA 1 as a novel factor promoting high-fat diet-induced obesity, at least partially, through modulating appetite-related genes ghrelin and PYY.