KDM4B protects against obesity and metabolic dysfunction

Proceedings of the National Academy of Sciences of the United States of America
Yingduan ChengCun-Yu Wang

Abstract

Although significant progress has been made in understanding epigenetic regulation of in vitro adipogenesis, the physiological functions of epigenetic regulators in metabolism and their roles in obesity remain largely elusive. Here, we report that KDM4B (lysine demethylase 4B) in adipose tissues plays a critical role in energy balance, oxidation, lipolysis, and thermogenesis. Loss of KDM4B in mice resulted in obesity associated with reduced energy expenditure and impaired adaptive thermogenesis. Obesity in KDM4B-deficient mice was accompanied by hyperlipidemia, insulin resistance, and pathological changes in the liver and pancreas. Adipocyte-specific deletion of Kdm4b revealed that the adipose tissues were the main sites for KDM4B antiobesity effects. KDM4B directly controlled the expression of multiple metabolic genes, including Ppargc1a and Ppara Collectively, our studies identify KDM4B as an essential epigenetic factor for the regulation of metabolic health and maintaining normal body weight in mice. KDM4B may provide a therapeutic target for treatment of obesity.

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Citations

Aug 4, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Changkeun KangHitoshi Okada
Feb 15, 2019·Genes·Cailin Wilson, Adam J Krieg
Jan 15, 2020·Journal of Experimental & Clinical Cancer Research : CR·Haijie LiXuelai Luo
May 23, 2020·Cell Proliferation·Yaqian ChenQuan Yuan
Jul 25, 2019·Frontiers in Genetics·Bruno Ramos-MolinaFrancisco J Tinahones
Aug 15, 2019·International Journal of Molecular Sciences·Geovanny I Nic-CanRafael A Rojas-Herrera
Jan 28, 2021·Epigenomics·Paolo E MacchiaPaola Ungaro
Jun 24, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sarder ArifuzzamanRabeya Khatun

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