Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance

Abstract

Aims/hypothesis Accumulating evidence suggests that maternal obesity may increase the risk of metabolic disease in the offspring. We investigated the effects of established maternal diet-induced obesity on male and female offspring appetite, glucose homeostasis and body composition in rats. Methods Female Wistar rats were fed either a standard chow (3% fat, 7% sugar [wt/wt]) or a palatable obesogenic diet (11% fat, 43% sugar [wt/wt]) for 8 weeks before mating and throughout pregnancy and lactation. Male and female offspring of control and obese dams were weaned on to standard chow and assessed until 12 months of age. Results At mating, obese dams were heavier than control with associated hyperglycaemia and hyperinsulinaemia. Male and female offspring of obese dams were hyperphagic (p<0.0001) and heavier than control (p<0.0001) until 12 months of age. NEFA were raised at 2 months but not at 12 months. At 3 months, OGTT showed more pronounced alteration of glucose homeostasis in male than in female offspring of obese animals. Euglycaemic-hyperinsulinaemic clamps performed at 8 to 9 months in female and 10 to 11 months in male offspring revealed insulin resistance in male offspring of obese dams (p<0.05 compared with control). Body compositional analysis at 12 months also showed increased fat pad weights in male and female offspring of obese animals. Conclusions/interpretation Diet-induced obesity in female rats leads to a state of insulin resistance in male offspring, associated with development of obesity and increased adiposity. An increase in food intake may play a role.

Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions

“…28 More recent studies have, therefore, used highly palatable or junk food diets in which the diets are rich in simple sugars as well as fat, reflective of an obesogenic western diet in humans. 33,34 Such junk food or cafeteria-style diets are suggested to provide a more representative model of the human situation for studies of maternal over-nutrition.…”

“…30,[33][34][35] Glucose intolerance and type 2 diabetes generally result from a combination of b-cell dysfunction and insulin resistance. There is good evidence that both of these contribute to the loss of glucose tolerance in the offspring of over-nourished dams.…”

“…Offspring of over-nourished dams also demonstrate insulin resistance. [33][34][35] This has been associated with altered expression of key components of the insulin-signaling pathway including insulin receptor substrate 1. 30,[37][38][39] The subsequent development of obesity could further increase the development of insulin resistance.…”

“…40 However, some studies suggest potential sex differences may be of interest to future investigations in which disturbed glucose homeostasis is a primary outcome. For example, two studies that use a highly palatable obesogenic diet have observed reduced glucose tolerance following intra-peritoneal glucose tolerance test 34 and insulin resistance assessed by hyperinsulinaemicFeuglycaemic clamp 33 in males but not female littermates. This is despite both sexes displaying elevated levels of adiposity compared with controls.…”

Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat

“…Recent clinical and experimental evaluations of the fetal origins of obesity (20,33), insulin resistance (33), and vascular dysfunction showed a role of sex in the issue (5, 50, 52). Until now, the sex-specific consequence was rarely taken into account in the evaluation of the long-term cellular and molecular effects of early poor protein restriction.…”