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      Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver.

      The Journal of Nutritional Biochemistry

      Adipose Tissue, metabolism, Animals, Diet, High-Fat, adverse effects, Fatty Liver, etiology, physiopathology, Female, I-kappa B Kinase, Insulin, blood, Insulin Resistance, Interleukin-1beta, JNK Mitogen-Activated Protein Kinases, Lactation, Liver, pathology, Male, Maternal Nutritional Physiological Phenomena, Mice, Obesity, Phosphorylation, Pregnancy, Sterol Esterase, Triglycerides, Tumor Necrosis Factor-alpha, Weaning

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          The exposure to an increased supply of nutrients before birth may contribute to offspring obesity. Offspring from obese dams that chronically consume a high-fat diet present clinical features of metabolic syndrome, liver lipid accumulation and activation of c-Jun N-terminal kinases (JNK) consistent with the development of nonalcoholic fatty liver disease (NAFLD). However, in spite of the importance of the resistance to insulin for the development of NAFLD, the molecular alterations in the liver of adult offspring of obese dams are yet to be investigated. In this study, we tested the hypothesis that the consumption of excessive saturated fats during pregnancy and lactation contributes to adult hepatic metabolic dysfunction in offspring. Adult male offspring of dams fed a high-fat diet (HN) during pregnancy and lactation exhibited increased fat depot weight; increased serum insulin, tumor necrosis factor α and interleukin 1β; and reduced serum triglycerides. Liver showed increased JNK and I kappa B kinase phosphorylation and PEPCK expression in the adult. In addition, liver triglyceride content in the offspring 1 week after weaning and in the adult was increased. Moreover, basal ACC phosphorylation and insulin signaling were reduced in the liver from the HN group as compared to offspring of dams fed a standard laboratory chow (NN). Hormone-sensitive lipase phosphorylation (Ser565) was reduced in epididymal adipose tissue from the HN group as compared to the NN group. It is interesting that all changes observed were independent of postweaning diet in 14-week-old offspring. Therefore, these data further reinforce the importance of maternal nutrition to adult offspring health. Copyright © 2012 Elsevier Inc. All rights reserved.

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