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Maternal obesity and gestational diabetes predispose the next generation to metabolic disturbances. Moreover, the lactation phase also stands as a critical phase for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here, we investigate the consequences of a maternal lipid-rich diet during gestation and lactation and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that was fed a standard diet during the gestation and lactation periods and an overnutrition group that was fed a high-fat diet (HF, 60% lipid-rich) during the same phases. The offspring were analyzed at postnatal days 21 and 28 and at 2 months old (PD21, PD28, and PD60) for their metabolic profiles (weight, fasting glycemia insulin sensitivity, and glucose tolerance) and euthanized for brain collection to evaluate metabolism and inflammation in the hypothalamus, hippocampus, and prefrontal cortex using Western blot markers of synaptic dynamics. At 2 months old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observed that the female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuated with age. In the offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. The offspring of the HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, the offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to an HF diet during pregnancy and lactation induces dysmetabolism in the offspring and is accompanied by heightened stress and anxiety. There was sexual dimorphism in the metabolic traits but not behavioral phenotypes.

Animal experimentation has a long history in the study of metabolic syndrome-related disorders. However, no consensus exists on the best models to study these syndromes. Knowing that different diets can precipitate different metabolic disease phenotypes, herein we characterized several hypercaloric rat models of obesity and type 2 diabetes, comparing each with a genetic model, with the aim of identifying the most appropriate model of metabolic disease. The effect of hypercaloric diets (high fat (HF), high sucrose (HSu), high fat plus high sucrose (HFHSu) and high fat plus streptozotocin (HF+STZ) during different exposure times (HF 3 weeks, HF 19 weeks, HSu 4 weeks, HSu 16 weeks, HFHSu 25 weeks, HF3 weeks + STZ) were compared with the Zucker fatty rat. Each model was evaluated for weight gain, fat mass, fasting plasma glucose, insulin and C-peptide, insulin sensitivity, glucose tolerance, lipid profile and liver lipid deposition, blood pressure, and autonomic nervous system function. All animal models presented with insulin resistance and dyslipidemia except the HF+STZ and HSu 4 weeks, which argues against the use of these models as metabolic syndrome models. Of the remaining animal models, a higher weight gain was exhibited by the Zucker fatty rat and wild type rats submitted to a HF diet for 19 weeks. We conclude that the latter model presents a phenotype most consistent with that observed in humans with metabolic disease, exhibiting the majority of the phenotypic features and comorbidities associated with type 2 diabetes in humans.