title: Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring.
abstract: Both epidemiologic and experimental animal studies demonstrate that chronic psychological stress exerts adverse effects on the initiation and/or progression of many diseases. However, intergenerational effects of this environmental information remains poorly understood. Here, using a C57BL/6 mouse model of restraint stress, we show that offspring of stressed fathers exhibit hyperglycemia due to enhanced hepatic gluconeogenesis and elevated expression of PEPCK. Mechanistically, we identify an epigenetic alteration at the promoter region of the Sfmbt2 gene, a maternally imprinted polycomb gene, leading to a downregulation of intronic microRNA-466b-3p, which post-transcriptionally inhibits PEPCK expression. Importantly, hyperglycemia in F1 mice is reversed by RU486 treatment in fathers, and dexamethasone administration in F0 mice phenocopies the roles of restraint stress. Thus, we provide evidence showing the effects of paternal psychological stress on the regulation of glucose metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers.
authors.affiliation: Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University School of Medicine, 16 North Guilin Road, Huangshi, Hubei 435003, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Shangang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Dongbao
authors.initials: D
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China. Electronic address: chenxuejin@shsmu.edu.cn.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China. Electronic address: lixy@sibs.ac.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D019175:DNA Methylation; D005786:Gene Expression Regulation; D005943:Gluconeogenesis; D006943:Hyperglycemia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D035683:MicroRNAs; C576133:Mirn466 microRNA, mouse; D012097:Repressor Proteins; C527638:Sfmbt2 protein, mouse; D014157:Transcription Factors; D019764:Phosphoenolpyruvate Carboxykinase (ATP)