Abstract
AIMS/HYPOTHESIS: Gestational exposures such as dietary changes can alter offspring phenotype through epigenetic modifications and promote increased risk for specific diseases, such as metabolic syndrome. We hypothesized that high-fat diet (HFD) during late gestation would lead increased risk for insulin resistance and hyperlipidemia via associated epigenetic alterations in tissue adipocytokine genes. METHODS: Offspring mice of mothers fed a HFD during late gestation (HFDO) were weighed and their food intake measured weekly till age 20 weeks at which time glucose and insulin tolerance tests, plasma lipid and adipocytokine levels were assessed, as well as mRNA expression in visceral fat. Adipocytokine gene methylation levels in visceral fat, liver and muscle were also assayed. RESULTS: HFDO mice had increased weight accrual and food intake, and exhibited insulin resistance, hyperlipidemia and hyperleptinemia, as well as hypoadiponectinemia. Furthermore, increased methylation of adiponectin and leptin receptor, and decreased methylation of leptin genes with unchanged glucagon-like peptide-1 methylation patterns emerged in HFDO mice. CONCLUSIONS: Taken together, late gestational HFD induces increased risk of metabolic syndrome in the progeny, which is coupled with hypoadiponectinemia as well as with leptin resistance, and concomitant presence of selective tissue-based epigenetic changes among adipocytokine genes.