Multigenerational effects of dietary macronutrient intake on the metabolic phenotype of male Wistar rats

•All diets cause distinct phenotypes attributable to the macronutrient constituents of the diet.•Phenotypes are consistent in succeeding generations.•The effects of the diet-induced phenotypes can be heightened in succeeding generations.•Quantity of diet consumed could have an effect on development of phenotype, especially as it affects gestational weight.•Macronutrient composition, not caloric content, is a major factor in development of phenotypes. Gene–nutrient interactions are implicated in metabolic phenotypes like metabolic syndrome. The aim of this study was to examine the effects of diet-induced metabolic phenotypes in rats and investigate the effects of these phenotypes in three successive generations. Three generations of rats were fed on different diets and mated. Blood glucose, adiposity, lipid profile, insulin, adipocytokines, ghrelin, and corticosterone concentrations were determined in F0, F1, and F2 generations using standard methods. In comparison with control across generations, glucose (32%), triacylglycerols (52%), and insulin (10%) were significantly elevated in the high-fat diet (HFD)-fed rats; total cholesterol was higher in HFD and high-carbohydrate diet (HCD)-fed groups; whereas high density lipoprotein was higher in the HFD rats but lower in the HPD rats. Adipocytokines were significantly higher in the HCD and HFD groups but lower in the high-protein diet group, whereas ghrelin only declined in HFD rats. This study revealed that different dietary macronutrients induced distinctive metabolic phenotypes, which had variable effects in different generations.