Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway.
Xinxing Wan, Linghao Wang, Md Asaduzzaman Khan, Lin Peng, Keke Zhang, Xiaoying Sun, Xuan Yi, Zhouqi Wang, Ke Chen
Author Information
Xinxing Wan: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China. ORCID
Linghao Wang: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China. ORCID
Md Asaduzzaman Khan: Department of Biochemistry and Microbiology, North South University, Dhaka, 1229, Bangladesh. ORCID
Lin Peng: Department of Nephrology, The First Hospital of Changsha, Changsha, 410005, Hunan, PR China. ORCID
Keke Zhang: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China. ORCID
Xiaoying Sun: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China. ORCID
Xuan Yi: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China.
Zhouqi Wang: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China. ORCID
Ke Chen: Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, PR China. chenke520@yeah.net. ORCID
The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.
