High‐fat high‐sucrose diet leads to dynamic structural and inflammatory alterations in the rat vastus lateralis muscle

Abstract

The influence of obesity on muscle integrity is not well understood. The purpose of this study was to quantify structural and molecular changes in the rat vastus lateralis (VL) muscle as a function of a 12-week obesity induction period and a subsequent adaptation period (additional 16-weeks). Male Sprague-Dawley rats consumed a high-fat, high-sucrose (DIO, n = 40) diet, or a chow control-diet (n = 14). At 12-weeks, DIO rats were grouped as prone (DIO-P, top 33% of weight change) or resistant (DIO-R, bottom 33%). Animals were euthanized at 12- or 28-weeks on the diet. At sacrifice, body composition was determined and VL muscles were collected. Intramuscular fat, fibrosis, and CD68+ cells were quantified histologically and relevant molecular markers were evaluated using RT-qPCR. At 12- and 28-weeks post-obesity induction, DIO-P rats had more mass and body fat than DIO-R and chow rats (p < 0.05). DIO-P and DIO-R rats had similar losses in muscle mass, which were greater than those in chow rats (p < 0.05). mRNA levels for MAFbx/atrogin-1 were reduced in DIO-P and DIO-R rats at 12- and 28-weeks compared to chow rats (p < 0.05), while expression of MuRF1 was similar to chow values. DIO-P rats demonstrated increased mRNA levels for pro-inflammatory mediators, inflammatory cells, and fibrosis compared to DIO-R and chow animals, despite having similar levels of intramuscular fat. The down-regulation of MAFbx/atrogin-1 may suggest onset of degenerative changes in VL muscle integrity of obese rats. DIO-R animals exhibited fewer inflammatory changes compared to DIO-P animals, suggesting a protective effect of obesity resistance on local inflammation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2069-2078, 2016.

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

“…In contrast to the sustained alterations in the VL muscle, the dynamic alterations observed in local gene expression, systemic inflammation and the gut microbiota early in the obesity induction phase could represent a reciprocal, dynamic competition of perturbations, which ultimately fails. This failure may initiate the process leading to obesity and compromised muscle integrity, potentially setting the stage for which progressive, chronic musculoskeletal alterations with obesity may be established11. Although the present study was not designed to evaluate direct causal or mechanistic relationships between metabolic challenge and muscle integrity, the insight gained through this integrated investigation provides critical understanding for the role of obesity on altered muscle integrity.…”

“…A tightening of such variation at 28-days suggests that a threshold may have been reached beyond which muscle repair is difficult. Therefore, 28-days on the HFS diet may prove to be an important time-point to determine whether muscle damage may still be reversible11.…”

“…Staining procedures for Oil Red O (ORO, intramuscular lipid), picrosirius red (collagen), and CD68+ cells were performed according to previous methods, and detailed procedures can be found elsewhere11. For ORO and picrosirius red, stained sections were imaged at 10x magnification and analyzed using a custom MatLab program11.…”

“…Over time, increased intramuscular lipid content leads to decreased muscle protein anabolism and compromised muscle repair, resulting in long term, dynamic, and pronounced decreases in muscle integrity3. Although alterations in muscle integrity have been observed after a standard obesity induction period11, the manner in which muscle morphological changes occur early in the induction phase of diet-induced obesity remain unclear, as few studies focus on elucidating early atrophy-related changes and aberrant repair processes with metabolic challenge512.…”

“…Cross-talk has been observed between adipose tissue and skeletal muscle during obesity onset14. Both mechanically and biologically, infiltration of fat and fibrosis in muscle tissue can compromise function, insulin sensitivity and biological homeostasis within the muscle311. However, the determinants of this intramuscular fibrosis, or whether this fibrosis relates to intramuscular adipose tissue deposits, are unclear, particularly early in the induction phase of diet-induced obesity314.…”