Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring

Paternal diet linked to glucose intolerance in daughters Childhood obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. A study in rats shows that normal females mated with obese, glucose-intolerant fathers on a high-fat diet produce female offspring who develop glucose intolerance due to impaired insulin secretion and pancreatic function. This is the first report in any species that a father's diet can initiate progression to diabetes in his offspring. The work highlights a novel role for environmentally induced paternal factors in influencing metabolic disease in offspring and in the growing epidemics of obesity and diabetes. Here it is shown that the consumption of a high-fat diet by male rats has an intergenerational effect: it leads to the dysfunction of pancreatic β-cells in female offspring. Relative to controls, these offspring showed an early onset of impaired insulin secretion and glucose tolerance, which worsened with time. The results add to our understanding of the complex genetic and environmental factors that are leading to the global epidemic of obesity and type 2 diabetes. The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic 1 , 2 . Having either parent obese is an independent risk factor for childhood obesity 3 . Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established 4 , the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs β-cell ‘dysfunction’ in rat F 1 female offspring. Chronic HFD consumption in Sprague–Dawley fathers induced increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had an early onset of impaired insulin secretion and glucose tolerance that worsened with time, and normal adiposity. Paternal HFD altered the expression of 642 pancreatic islet genes in adult female offspring ( P