A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats.

Jaqueline L Rios,David A Hart,Walter Herzog,Kelsey H Collins,Ian C Smith,Raylene A Reimer,Ruth A Seerattan,Heather A Paul

doi:10.1038/srep37278

Abstract

The chronic low-level inflammation associated with obesity is known to deleteriously affect muscle composition. However, the manner in which obesity leads to muscle loss has not been explored in detail or in an integrated manner following a short-term metabolic challenge. In this paper, we evaluated the relationships between compromised muscle integrity, diet, systemic inflammatory mediators, adipose tissue, and gut microbiota in male Sprague-Dawley rats. We show that intramuscular fat, fibrosis, and the number of pro-inflammatory cells increased by 3-days and was sustained across 28-days of high-fat high-sugar feeding compared to control-diet animals. To understand systemic contributors to muscle damage, dynamic changes in gut microbiota and serum inflammatory markers were evaluated. Data from this study links metabolic challenge to persistent compromise in muscle integrity after just 3-days, a finding associated with altered gut microbiota and systemic inflammatory changes. These data contribute to our understanding of early consequences of metabolic challenge on multiple host systems, which are important to understand as obesity treatment options are developed. Therefore, intervention within this early period of metabolic challenge may be critical to mitigate these sustained alterations in muscle integrity.

Highlights

Adipose tissue lipid storage is altered with obesity, and adipose tissue fibrosis is considered a hallmark of metabolic alterations on adipose tissue[3,13]
The purpose of the present set of studies was to determine the time-course of vastus lateralis (VL) intramuscular fat accumulation and development of fibrosis, in conjunction with short-term systemic, tissue, gut microbial, and molecular alterations following a short-term HFS metabolic challenge
Based on the data from this study, we suggest that a link exists between HFS metabolic challenge and persistent increases in intramuscular fat, fibrosis, and CD68+inflammatory cell number in the VL muscle by 3-days on an HFS diet, the specific mediator(s) responsible remain to be determined

Summary

Introduction

Adipose tissue lipid storage is altered with obesity, and adipose tissue fibrosis is considered a hallmark of metabolic alterations on adipose tissue[3,13]. The purpose of the present set of studies was to determine the time-course of vastus lateralis (VL) intramuscular fat accumulation and development of fibrosis, in conjunction with short-term systemic (inflammatory cytokines), tissue (adipose tissue and VL muscle), gut microbial, and molecular alterations (inflammation, oxidative stress) following a short-term HFS metabolic challenge. These data will provide a framework linking system-wide changes early in the inductive phase of obesity that result in compromised muscle integrity[12]

Methods

Results

Conclusion