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Publication
Maternal exposure to high-fat diet during pregnancy and lactation predisposes
normal weight offspring mice to develop hepatic inflammation and insulin
resistance.
Authors Saengnipanthkul S, Noh HL, Friedline RH, Suk S, Choi S, Acosta NK, Tran DA, Hu
X, Inashima K, Kim AM, Lee KW, Kim JK
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Physiological reports
Year 2021
Date Published 3/1/2021
Volume : Pages 9 : e14811
PubMed Reference 33769706
Abstract Increasing 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-1ß, 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.




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