The global prevalence of overweight and obesity is rising alarmingly, with almost two thirds of adults overweight or obese in most western countries. Parental obesity is a major predictor of child obesity. While the impact of maternal obesity on offspring metabolism is well documented, strong evidence for a paternal obesity influence is just emerging. Our laboratory is examining the contribution of both maternal and paternal obesity to offspring outcomes in the rat.

Female Sprague Dawley rats were fed normal chow or high fat diet (HFD) ad libitum for 6 weeks; dams consumed the same diet throughout gestation and lactation. At weaning, rats were separated into chow or HFD groups. In some studies half of each group was given running wheels while the remainder were sedentary.  Rats were killed at day 1, weaning or 15 weeks for blood, fat, liver and hypothalamus collection.

Maternal dietary obesity led to increased body weight and adiposity in offspring, which was exacerbated if offspring themselves consumed HFD. Alterations in hypothalamic appetite mediators included reduced mRNA expression of NPY, POMC, leptin receptor and STAT3. Thus early in life appetite regulators are affected by intrauterine overnutrition and this may contribute to eating disorders later in life.  When half of the offspring were provided with a running wheel, exercise had no impact in chow fed offspring of lean dams, but reduced the detrimental effects of maternal obesity in both chow and HFD-fed offspring, decreasing body weight, adiposity, plasma leptin and insulin concentrations.

Paternal obesity also influenced offspring metabolic risk (Ng et al, 2010), reducing glucose tolerance and insulin secretion, associated with altered islet gene expression. Our challenge is to define the mechanisms underlying the effects of parental obesity on offspring, and to investigate which epigenetic mechanisms mediate the transgenerational effects.