Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance
Noh, Hye Lim
Friedline, Randall H.
Acosta, Nicholas K.
Tran, Duy A.
Kim, Allison M.
Lee, Ki Won
Kim, Jason K.
UMass Chan AffiliationsDivision of Endocrinology, Metabolism, and Diabetes, Department of Medicine
Program in Molecular Medicine
Biochemical Phenomena, Metabolism, and Nutrition
Dietetics and Clinical Nutrition
Endocrinology, Diabetes, and Metabolism
Maternal and Child Health
Nutritional and Metabolic Diseases
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AbstractIncreasing evidence shows a potential link between the perinatal nutrient environment and metabolic outcome in offspring. Here, we investigated the effects of maternal feeding of a high-fat diet (HFD) during the perinatal period on hepatic metabolism and inflammation in male offspring mice at weaning and in early adulthood. Female C57BL/6 J mice were fed HFD or normal chow (NC) for 4 weeks before mating and during pregnancy and lactation. The male offspring mice were weaned onto an NC diet, and metabolic and molecular experiments were performed in early adulthood. At postnatal day 21, male offspring mice from HFD-fed dams (Off-HFD) showed significant increases in whole body fat mass and fasting levels of glucose, insulin, and cholesterol compared to male offspring mice from NC-fed dams (Off-NC). The RT-qPCR analysis showed two- to fivefold increases in hepatic inflammatory markers (MCP-1, IL-1beta, and F4/80) in Off-HFD mice. Hepatic expression of G6Pase and PEPCK was elevated by fivefold in the Off-HFD mice compared to the Off-NC mice. Hepatic expression of GLUT4, IRS-1, and PDK4, as well as lipid metabolic genes, CD36, SREBP1c, and SCD1 were increased in the Off-HFD mice compared to the Off-NC mice. In contrast, CPT1a mRNA levels were reduced by 60% in the Off-HFD mice. At postnatal day 70, despite comparable body weights to the Off-NC mice, Off-HFD mice developed hepatic inflammation with increased expression of MCP-1, CD68, F4/80, and CD36 compared to the Off-NC mice. Despite normal body weight, Off-HFD mice developed insulin resistance with defects in hepatic insulin action and insulin-stimulated glucose uptake in skeletal muscle and brown fat, and these metabolic effects were associated with hepatic inflammation in Off-HFD mice. Our findings indicate hidden, lasting effects of maternal exposure to HFD during pregnancy and lactation on metabolic homeostasis of normal weight offspring mice.
Saengnipanthkul S, Noh HL, Friedline RH, Suk S, Choi S, Acosta NK, Tran DA, Hu X, Inashima K, Kim AM, Lee KW, Kim JK. Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance. Physiol Rep. 2021 Mar;9(6):e14811. doi: 10.14814/phy2.14811. PMID: 33769706; PMCID: PMC7995551. Link to article on publisher's site