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 previously showed short-term (4 weeks) HED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of gut-brain vagal communication. Objectives: To investigate the effect of long-term (6 months) HED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the nucleus of the solitary tract (NTS), and systemic inflammation. Methods: Male Sprague-Dawley rats were fed a low energy density (LED) diet for 2 weeks then switched to HED for 26 weeks. Food intake, body weight, and body composition were measured twice weekly; serum and fecal samples were collected at baseline, 1, 4, 8, and 26 weeks. Serum insulin, leptin, and cytokines were measured by ELISA; fecal microbiota profiled by 16S rRNA sequencing. Results: HED induced microbiota dysbiosis within 1 week of diet introduction. Significant microglia activation in the intermediate NTS and marked hepatic lipidosis appeared after 4 weeks. Changes in serum cytokine profile were evident after 26 weeks of HED feeding. Conclusions: Microbiota dysbiosis is the earliest response to HED diets, followed by increased liver fat accumulation, microglia activation in the brain, and elevated circulating inflammatory markers. This study presents longitudinal and cross-sectional results on long-term HED effects on these parameters in a single cohort of animals.