Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic perturbations

Zhiguo Liu, Chun Yan Lim, Michelle Yu Fah Su, Stephanie Li Ying Soh, Guanghou Shui, Markus R. Wenk, Kevin L. Grove, George K. Radda, Weiping Han, Xiaoqiu Xiao

    Research output: Contribution to journalArticle

    18 Scopus citations

    Abstract

    Neonatal overnutrition results in accelerated development of high-fat diet (HFD)-induced metabolic defects in adulthood. To understand whether the increased susceptibility was associated with aggravated inflammation and dysregulated lipid metabolism, we studied metabolic changes and insulin signaling in a chronic postnatal overnutrition (CPO) mouse model. Male Swiss Webster pups were raised with either three pups per litter to induce CPO or ten pups per litter as control (CTR) and weaned to either low-fat diet (LFD) or HFD. All animals were killed on the postnatal day 150 (P150) except for a subset of mice killed on P15 for the measurement of stomach weight and milk composition. CPO mice exhibited accelerated body weight gain and increased body fat mass prior to weaning and the difference persisted into adulthood under conditions of both LFD and HFD. As adults, insulin signaling was more severely impaired in epididymal white adipose tissue (WAT) from HFD-fed CPO (CPO-HFD) mice. In addition,HFD-induced upregulation of pro-inflammatory cytokines was exaggerated in CPO-HFD mice. Consistent with greater inflammation, CPO-HFD mice showed more severe macrophage infiltration than HFD-fed CTR (CTR-HFD) mice. Furthermore, when compared with CTR-HFD mice, CPO-HFD mice exhibited reduced levels of several lipogenic enzymes in WAT and excess intramyocellular lipid accumulation. These data indicate that neonatal overnutrition accelerates the development of insulin resistance and exacerbates HFD-induced metabolic defects, possibly by worsening HFD-induced inflammatory response and impaired lipid metabolism.

    Original languageEnglish (US)
    Pages (from-to)131-143
    Number of pages13
    JournalJournal of Endocrinology
    Volume219
    Issue number2
    DOIs
    StatePublished - Oct 22 2013

      Fingerprint

    Keywords

    • Adipose tissue
    • Fatty acids
    • Glucose transport
    • Insulin resistance
    • Obesity

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

    Cite this

    Liu, Z., Lim, C. Y., Su, M. Y. F., Soh, S. L. Y., Shui, G., Wenk, M. R., Grove, K. L., Radda, G. K., Han, W., & Xiao, X. (2013). Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic perturbations. Journal of Endocrinology, 219(2), 131-143. https://doi.org/10.1530/JOE-13-0111