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Hypothalamic expression of genes for appetite regulators and estrogen α, estrogen β and leptin receptors in obese dams and their fetuses

  • A. B. Breton (a1), R. R. Cockrum (a1), K. J. Austin (a1), K. M. Cammack (a1), S. P. Ford (a2), B. W. Hess (a1), G. E. Moss (a1), P. W. Nathanielsz (a3) and B. M. Alexander (a1)...

Abstract

Under- and over-nutrition during gestation may influence fetal hypothalamic development resulting in individuals predisposed to adverse health effects. This study examined fetuses from obese and control ewes to determine whether dam obesity alters hypothalamic expression of fetal appetite regulatory genes. A second objective was to contrast the expression of appetite regulatory genes in ewes that become the most obese to those that remained in moderate body condition on the same energy-rich diet. Multiparous, western white-faced ewes were weighed and individually fed 100% (control) or 150% (obese) of National Research Council requirements from day 60 before mating until day 75 of gestation. At day 75 of gestation, fetuses were collected and weighed. Hypothalamic tissue from fetal lambs and dams was collected and frozen for mRNA extraction. Dam obesity (P ⩾ 0.16), fetal sex (P ⩾ 0.44) or their interaction (P ⩾ 0.42) did not affect the relative expression of fetal hypothalamic regulators of appetite, including neuropeptide Y, agouti-related protein, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript and receptors for leptin. Maternal obesity at day 75 of gestation in ewes did not affect developmental mechanisms responsible for the expression of fetal appetite regulatory genes and would not be expected to predispose offspring to adult-onset obesity through disrupted appetite regulation at this developmental time point. In the ewe, appetite regulatory genes did not differ (P > 0.20) with ewe adiposity; however, expression of estrogen receptor α, but not β (P = 0.37), in the medial basal hypothalamus was greater (P = 0.04) in obese than in control ewes.

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