The Beneficial Effects of Early Short‐Term Exercise in the Offspring of Obese Mothers are Accompanied by Alterations in the Hypothalamic Gene Expression of Appetite Regulators and FTO (Fat Mass and Obesity Associated) Gene

Abstract

Maternal overnutrition is implicated in the development of adult metabolic disease, and has been shown to alter the expression of genes involved in energy homeostasis. In the present study, we aimed to test whether a short period of voluntary exercise, followed by a sedentary period, would regulate hypothalamic markers involved in appetite. Adult female Sprague-Dawley rats were fed either normal chow or high-fat diet (HFD) ad lib. for 5 weeks, mated and continued on their assigned diet during gestation/lactation. At weaning males, were separated into chow or HFD groups; half were exercised (running wheels), whereas the remainder were sedentary. At week 10, wheels were removed and rats remained sedentary for 5 weeks, prior to tissue collection. Maternal obesity increased offspring adiposity at 15 weeks and this was exacerbated by postnatal HFD (P < 0.05). Body weight and fat mass were reduced in offspring of obese mothers if they exercised, and this was maintained even after 5 weeks without exercise. At 15 weeks, fasting plasma insulin, leptin and triglyceride concentrations were significantly reduced by exercise in offspring of lean and obese mothers consuming chow, with little benefit in those consuming HFD. Hypothalamic mRNA expression of pro-opiomelanocortin was increased by exercise but only in offspring of lean mothers. Exercise reduced hypothalamic FTO (fat mass and obesity associated) mRNA in offspring of lean dams regardless of diet. A short period of exercise early in life had lasting beneficial effects on body weight, adiposity and hormone profile of male offspring from obese and lean dams, despite being followed by a period of inactivity. The effects of exercise on hypothalamic appetite regulators were more marked in offspring of lean dams.

Maternal obesity regulates gene expression in the hearts of offspring

“…Thus it would appear that cardiac FTO expression is affected by obesity and maternal programming, making it another interesting candidate gene for the CVD risk observed with maternal M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT obesity. FTO expression was also regulated by exercise; our lab has previously shown an effect of exercise on FTO expression in the hypothalamus [30], and here maternal exercise increased FTO expression in offspring of dams consuming chow.…”

Human obesity: FTO, IRX3, or both?

“…Although no differences in central nervous system FTO gene expression between FTO genotypes in the cerebellum were found, there was indeed inter-individual variance in the FTO expression in this examined brain region [1]. Previous studies in mice have shown that the CNS expression of Fto can be weakened by exercise protocols [9]. This may also explain why population-based studies have shown that regular exercise attenuates the strength of the association between genetic variants in FTO and human obesity [10].…”

Complex Relationship between Obesity and the Fat Mass and Obesity Locus

“…FTO enhanced TCA cycle activity by regulating 2-oxoglutarate levels to promote differences in body energy metabolism 100. However, at present, there is another hypothesis that FTO may be a sensor of circulating amino acids rather than a sensor of 2-oxoglutarate 101-106. This action mainly occurs in FTO-deficient mice that exhibit developmental deformities.…”