Cleal, Jane, Bruce, Kimberley D., Shearer, Jasmine L., Thomas, Hugh, Plume, Jack, Gregory, Louise, Shepard, James, Spiers-Fitzgerald, Kerry, Mani, Ravi, Lewis, Rohan, Lillycrop, Karen, Hanson, Mark, Byrne, Christopher and Cagampang, Felino (2019) Maternal obesity during pregnancy alters daily activity and feeding cycles, and hypothalamic clock gene expression in adult male mouse offspring. International Journal of Molecular Sciences, 20 (21), 1-19, [5408]. (doi:10.3390/ijms20215408).
Abstract
An obesogenic diet adversely affects the endogenous mammalian circadian clock, altering daily activity and metabolism, and resulting in obesity. We investigated whether an obese pregnancy can alter the molecular clock in the offspring hypothalamus, resulting in changes to their activity and feeding rhythms. Female mice were fed a control (C, 7% kcal fat) or high fat diet (HF, 45% kcal fat) before mating and throughout pregnancy. Male offspring were fed the C or HF diet postweaning, resulting in four offspring groups: C/C, C/HF, HF/C, and HF/HF. Daily activity and food intake were monitored, and at 15 weeks of age were killed at six time-points over 24 h. The clock genes Clock, Bmal1, Per2, and Cry2 in the suprachiasmatic nucleus (SCN) and appetite genes Npy and Pomc in the arcuate nucleus (ARC) were measured. Daily activity and feeding cycles in the HF/C, C/HF, and HF/HF offspring were altered, with increased feeding bouts and activity during the day and increased food intake but reduced activity at night. Gene expression patterns and levels of Clock, Bmal1, Per2, and Cry2 in the SCN and Npy and Pomc in the ARC were altered in HF diet-exposed offspring. The altered expression of hypothalamic molecular clock components and appetite genes, together with changes in activity and feeding rhythms, could be contributing to offspring obesity.
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