n-3 PUFAs protect against adiposity and fatty liver by promoting browning in postnatally overfed male rats: a role for NRG4 |
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| Institution: | 1. Department of Child Health Care, Children''s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China;2. Institute of Pediatric Research, Nanjing Medical University, Nanjing, Jiangsu Province, China;1. Department of Food and Human Nutritional Sciences, University of Manitoba, Canada;2. Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada;3. School of Medicine, Federal University of Uberlândia, Brazil;4. Department of Physiology and Pathophysiology, University of Manitoba, Canada;1. Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan;3. Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan;4. Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, Taiwan;5. Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung, Taiwan;6. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;7. Division of Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;8. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan |
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| Abstract: | Early-life nutrition plays an important role in regulating adult metabolism. This study evaluated the effects of early nutrition during the suckling and postweaning periods on expression of the adipocytokine Neuregulin 4 (Nrg4) and its relationship with nonalcoholic fatty liver disease (NAFLD) in adulthood. In vivo, male rats were adjusted to litter sizes of three (small litter, SL) or ten (normal litter, NL) on postnatal day 3. Pups were fed control chow (NL and SL groups) or a high-fat diet (NL-HF and SL-HF groups), and SL pups specifically were fed a fish oil diet rich in n-3 polyunsaturated fatty acids (n-3 PUFAs) (SL-FO group), from postnatal weeks 3 to 13. The results demonstrated that postnatal overnutrition increased weight, hepatic de novo lipogenesis (DNL) gene expression and NAFLD and decreased body temperature and Nrg4, Ucp1 and Pgc1a mRNA expression in adipose tissues in SL, SL-HF and NL-HF rats compared to NL rats in adulthood. The opposite trends were observed in SL-FO rats. Moreover, in vitro, recombinant NRG4 protein reduced lipid accumulation by inhibiting DNL gene expression in fatty HepG2 cells stimulated with sodium oleate. In HPAs, eicosapentaenoic acid (EPA) treatment elevated NRG4 production and caused adipocyte browning, and these effects were abrogated by PPARG antagonism. In conclusion, a postweaning n-3 PUFA diet enhanced Nrg4 expression in adipose tissues, associated with attenuation of NAFLD induced by SL rearing. Additionally, external NRG4 reduced lipogenesis in steatotic hepatocytes. Thus, white adipose tissue browning induced by n-3 PUFAs may promote NRG4 production through the PPARG pathway. |
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