Maternal high fat diet induces circadian clock-independent endocrine alterations impacting the metabolism of the offspring
Lu Ding,
Benjamin D. Weger,
Jieying Liu,
Liyuan Zhou,
Yenkai Lim,
Dongmei Wang,
Ziyan Xie,
Jing Liu,
Jing Ren,
Jia Zheng,
Qian Zhang,
Miao Yu,
Meltem Weger,
Mark Morrison,
Xinhua Xiao,
Frédéric Gachon
Affiliations
Lu Ding
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Benjamin D. Weger
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Jieying Liu
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
Liyuan Zhou
Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100022, China
Yenkai Lim
Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD 4102, Australia
Dongmei Wang
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Ziyan Xie
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Jing Liu
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Jing Ren
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Jia Zheng
Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
Qian Zhang
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Miao Yu
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Meltem Weger
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Mark Morrison
Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD 4102, Australia; Australian Infectious Diseases Research Centre, St. Lucia, QLD 4072, Australia
Xinhua Xiao
Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Corresponding author
Frédéric Gachon
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia; Corresponding author
Summary: Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.