A long-term maternal diet intervention is necessary to avoid the obesogenic effect of maternal high-fat diet in the offspring |
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| Institution: | 1. Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202;2. Department of Nutrition and Food Sciences, Texas A&M University, College Station, TX 77843;3. Department of Pathology, University of North Dakota, Grand Forks, ND 58202;4. ND-INBRE Bioinfomatic Core, University of North Dakota, Grand Forks, ND 58202;5. Hubei Cancer Hospital, Wuhan, Hubei 430079, China;6. Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;7. Campus Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China;8. Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ, USA;9. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA;10. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA;1. Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan;2. Jinnouchi Clinic, Diabetes Care Center, Kumamoto, Japan;3. Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan;1. Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA;2. Department of Obstetrics, Gynecology and Reproductive Medicine, University of California San Francisco, San Francisco, CA;3. Institute for Human Genetics, Benioff Children''s Hospital San Francisco, University of California San Francisco, San Francisco, CA;1. Department of Pediatrics, Division of Neonatology & Developmental Biology, Neonatal Research Center of the UCLA Children''s Discovery and Innovation Institute, David Geffen School of Medicine UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1752;2. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, 9620 Carnegie Ave, Cleveland, OH 44106;1. Oncology Department, Shanghai Ninth People''s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China;2. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA |
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| Abstract: | Although a pre-pregnancy dietary intervention is believed to be able to prevent offspring obesity, research evidence is absent. We hypothesize that a long period of pre-pregnancy maternal diet transition from a high-fat (HF) diet to a normal-fat (NF) diet effectively prevents offspring obesity, and this preventive effect is independent of maternal body weight change. In our study, female mice were either continued on an NF diet (NF group) or an HF diet (HF group) until weaning, or switched from an HF to an NF for 1 week (H1N group), 5 weeks (H5N group) or 9 weeks (H9N group) before pregnancy. After weaning, the offspring were given the HF diet for 12 weeks to promote obesity. The mothers, regardless of which group, did not display maternal body weight change and glucose intolerance either before pregnancy or after weaning. Compared to the HF group, the H1N and H5N, but not the H9N, offspring developed glucose intolerance earlier, with more severely imbalanced glucose homeostasis. These offspring also displayed hepatocyte degeneration and significant adipocyte hypertrophy associated with higher expression of lipogenesis genes. The molecular mechanistic study showed blunted insulin signaling, overactivated adipocyte Akt signaling and hepatic AMPK signaling with enhanced lipogenesis genes in the H1N and H5N versus the NF offspring. However, maternal H9N diets normalized glucose and lipid metabolism of the offspring via resensitized insulin signaling and normalized Akt and AMPK signaling. In summary, we showed that a long-term maternal diet intervention effectively released the intergenerational obesogenic effect of maternal HF diet independent of maternal weight management. |
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