Endocrine Abstracts

Obesity and type II diabetes associated with obesity have reached epidemic proportions in both developed and underdeveloped countries. Epidemiological evidence has demonstrated that children born to obese women have a greater risk of developing obesity, insulin resistance and metabolic syndrome than those born to lean women. Leptin, an adipose tissue hormone, inhibits the brain’s central drive to eat, enabling maintenance of normal body weight and composition. In the rodent, a neonatal leptin spike plays a central role in regulating development of the hypothalamic appetite control centers. We have recently reported that obese overfed ewes exhibited markedly greater insulin resistance and elevated baseline blood glucose and insulin during pregnancy than ewes fed only to National Research Council (NRC) recommendations. Female F1 offspring born to these obese mothers (F1OM) exhibited markedly greater (P<0.01) adiposity at birth, as well as a failure to exhibit a leptin spike between 6 and 9 days of postnatal age as observed in F1 offspring of mothers fed only to NRC recommendations (F1RM). As adults, F1OM females exhibited an increased appetite, leading to increased weight gain, adiposity and insulin resistance when compared to F1RM females. To evaluate transgenerational impacts of maternal obesity, both mature F1OM and F1RM ewes were fed only to NRC recommendations throughout a gestation. From mid to late gestation, F1OM ewes exhibited markedly greater (P<0.01) baseline blood glucose and insulin than F1RM ewes, and were more insulin resistant. As observed for their mothers, F2 lambs born to F1OM ewes had a markedly greater (P<0.01) % body fat, and failed to exhibit the postnatal leptin spike exhibited by F2 lambs born to F1RM ewes. These data demonstrate a transgenerational impact of maternal diet-induced obesity on the F2 generation, and are consistent with a predisposition for increased appetite, adiposity and metabolic disease in adult life.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: National Institutes of Health Grant INBRE P20 RR16474.