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

Dulce M Minaya,Andras Hajnal,Anna Turlej,Abhinav Joshi,Tamas Nagy,Noah Weinstein,Krzysztof Czaja,Patricia Dilorenzo

doi:10.1038/s41387-020-0119-4

Abstract

IntroductionObesity 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.ObjetivesThe 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.MethodsMale 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.ResultsHED 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.ConclusionsThese 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.

Highlights

Obesity is a multifactorial chronic inflammatory disease
We further observed changes in the serum cytokine profile after 26 weeks of high energy density (HED) feeding. 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
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

Summary

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. Consumption of high energy density (HED) diets triggers microbiota dysbiosis, increased body fat accumulation, and metabolic syndrome[1,2]. Once thought to be inert, adipose tissue is recognized as a metabolically active endocrine organ[3] This enlargement occurs through an increase in the number of adipocytes (adipogenesis) or an increase in the size of existing adipocytes (hypertrophy)[4]. In the db/db mouse model, there is a high number of adipogenic/angiogenic cell clusters in the early stages of obesity The number of these cell clusters declines over time and there is an increase in the number of crown-like structures, which are hallmarks of local infiltration of macrophages into tissue surrounding dead adipocytes[5]. It would appear that the tonic activation of the innate immune system induced by excess energy intake gradually disrupts the homeostatic state, triggering chronic inflammation

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