Consumption of a high energy density diet triggers microbiota dysbiosis, hepatic lipidosis, and microglia activation in the nucleus of the solitary tract in rats.

INTRODUCTION: Obesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (HED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a HED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication. OBJETIVES: The aim of this study was to investigate the effect of long-term (6 months) consumption of HED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the nucleus of the solitary tract, and systemic inflammation. METHODS: Male Sprague-Dawley rats were fed a low energy density (LED) diet for 2 weeks and then switched to a HED diet for 26 weeks. Twenty-four-hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, 1, 4, 8, and 26 weeks after introduction of the HED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were assessed for 16 S rRNA genome sequencing. RESULTS: HED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after 4 weeks of HED diet. We further observed changes in the serum cytokine profile after 26 weeks of HED feeding. CONCLUSIONS: These data suggest that microbiota dysbiosis is the first response of the organism to HED diets, followed by increased liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers. To our knowledge, this is the first study to present longitudinal and cross-sectional results on effect of long-term consumption of HED diets on all these parameters in a single cohort of animals.

Congenital brain dysplasias of different genesis can differently affect susceptibility to pilocarpine- or kainic acid-induced seizures in the rat.

Interruption of neurogenesis and/or neuronal migration produces brain dysplasia modifying susceptibility to epileptic seizures in adulthood. The course of neurogenesis has a strictly defined time-table. Consequently, the developmental stage at which the interruption occurs determines what functional subsystem potentially involved in epileptogenesis will suffer from irreversible neuronal deficit. The present study attempts to verify a hypothesis that brain dysplasias of different genesis should also lead to different susceptibility to seizures evoked by receptor agonists of different functional specificity, like kainic acid or pilocarpine, a cholinergic or glutaminergic agonist, respectively. Pregnant Wistar rats were exposed to gamma-rays on gestation days 13, 15, 17 or 19 (E13, E15, E17 or E19). Sixty-day-old offsprings of the females were injected with kainic acid or pilocarpine to evoke status epilepticus. During a 6-h period following the injection, motor manifestations of seizure activity were recorded. Generally, the intensity of pilocarpine-induced symptoms was relatively low in rats irradiated on E13 or E15 but high in rats irradiated on E17 or E19. In rats treated with kainic acid, the trend was opposite, viz. the later the prenatal irradiation was performed, the less intense epileptic symptoms were induced in adulthood. The data provide evidence that dysplasias acquired during prenatal development may significantly amplify or reduce the brain susceptibility to seizures. However, this relation depends not only on the developmental stage at which the dysplasias were produced but also on the functional specificity of epileptogenic stimuli used in the experimental model of epilepsy.