Maternal high‐fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning

Key points•  Perinatal maternal high‐fat diet changes milk composition, resulting in obesity and hyperglycaemia in male offspring at weaning. •  Offspring obesity is associated with hyperleptinaemia and changes in the central leptin signalling pathway in the hypothalamic arcuate nucleus. •  Maternal high‐fat diet increased adrenal catecholamines in offspring but reduced liver and adipose tissue adrenoreceptors, thereby contributing to increased adiposity in these animals. •  Early obesity and hyperleptinaemia in offspring may have a stimulatory effect on the hypothalamus–pituitary–thyroid axis as an adaptive response to the positive energy balance. •  Both catecholamines and thyroid hormones may impact cardiovascular function, thereby contributing to the development of hypertension.Abstract  Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high‐fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high‐fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3‐adrenoreceptor content in adipose tissue (−40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p‐STAT3/STAT3 (−40%, P < 0.05) and SOCS3 (−55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases maternal body fat and this additional energy is transferred to the offspring during lactation, since at weaning the dams had normal fat and the pups were obese. The higher fat and protein concentrations in the breast milk seemed to induce early overnutrition in the HF offspring. In addition to storing energy as fat, the HF offspring had a larger reserve of glycogen and hyperglycaemia that may have resulted from increased gluconeogenesis. Hyperleptinaemia may stimulate both adrenal medullary and thyroid function, which may contribute to the development of cardiovascular diseases. These early changes induced by the maternal high‐fat diet may contribute to development of metabolic syndrome.