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Activating transcription factor 3, glucolipid metabolism, and metabolic diseases 
Shuwei Hu1,† , Xiaojie Zhao2,† , Rui Li2 , Chencheng Hu2 , Huijuan Wu2 , Jing Li3,* , Yanqiao Zhang1,* , Yanyong Xu4,5,*
1Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA
2Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
3Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, China
4Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Pathology of School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
5Frontier Innovation Center, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
These authors contributed equally to this work.
*Correspondence to:Jing Li , Yanqiao Zhang , Yanyong Xu ,
J Mol Cell Biol, Volume 14, Issue 10, October 2022, mjac067,
Keyword: ATF3, glucolipid metabolism, metabolic organ, metabolic diseases

Lipids and glucose exert many essential physiological functions, such as providing raw materials or energy for cellular biosynthesis, regulating cell signal transduction, and maintaining a constant body temperature. Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases, such as obesity, diabetes, and cardiovascular disease. Therefore, intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases. Activating transcription factor 3 (ATF3) is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation, apoptosis, DNA repair, and oncogenesis. Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism. ATF3 inhibits intestinal lipid absorption, enhances hepatic triglyceride hydrolysis and fatty acid oxidation, promotes macrophage reverse cholesterol transport, and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis. In addition to its role in lipid metabolism, ATF3 has also been identified as an important regulator of glucose metabolism. Here, we summarize the recent advances in the understanding of ATF3, mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.