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

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.