Obesity is a multifactorial chronic inflammatory disease. Consumption of energy-dense (E-D) 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 E-D diets triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal system. The aim of the current study was to investigate the effect of long-term (6 months) consumption of an E-D diet on food intake, body composition, gut microbiome, and the development of systemic inflammation.


Male Sprague-Dawley rats were fed regular chow for two weeks and then switched to an E-D (45% fat) diet for 26 weeks. 24h food intake, body weight, and body composition were measured twice a week. Blood serum was collected at baseline, and 4, 8, and 26 weeks after introduction of E-D diet to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were collected at baseline, and 1, 4, 8, and 26 weeks after introduction of E-D diet for 16S rRNA genome sequencing.


Our data revealed that roughly half of the animals gained significantly more body fat than the other half, in spite of similar caloric consumption. After four weeks of E-D consumption, insulin levels were significantly higher compared to baseline. Levels of leptin, MCP-1, and MIP-1a were significantly higher after 26 weeks of E-D diet. One week of E-D consumption decreased species diversity and increased the ratio of Firmicutes to Bacteroidetes, changes associated with an obese phenotype.


In conclusion, the data revealed that the rats exhibited a diet-induced obesity prone (DIO-P) or DIO-R (resistant) phenotype. However, there were no significant differences in cytokine levels and microbiome changes between DIO-R and DIO-P rats. This suggests that diet plays a larger role in the development of systemic inflammation than fat mass gained.