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 37 was to quantify structural and molecular changes in the rat vastus lateralis (VL) muscle as a 38 function of a 12-week obesity induction period and a subsequent adaptation period (additional 39 16-weeks). Male Sprague-Dawley rats consumed a high-fat, high-sucrose (DIO, n=40) diet or a 40 chow control-diet (n=14). At 12-weeks, DIO rats were grouped as prone (DIO-P, top 33% of 41 weight change) or resistant (DIO-R, bottom 33%). Animals were euthanized at 12-weeks or 28-42 weeks on the diet. At sacrifice, body composition was determined and VL muscles were 43 collected. Intramuscular fat, fibrosis, and CD68+ cells were quantified histologically and 44 relevant molecular markers were evaluated using RT-qPCR. At 12- and 28-weeks post obesity 45 induction, DIO-P rats had more mass and body fat than DIO-R and chow rats (p<0.05). DIO-P 46 and DIO-R rats had similar losses in muscle mass, which were greater than those in chow rats 47 (p<0.05). mRNA levels for MAFbx/atrogin1 were reduced in DIO-P and DIO-R rats at 12- and 48 28-weeks compared to chow rats (p<0.05), while expression of MURF was similar to chow 49 values. DIO-P rats demonstrated increased mRNA levels for pro-inflammatory mediators, 50 inflammatory cells, and fibrosis compared to DIO-R and chow animals, despite having similar 51 levels of intramuscular fat. The down-regulation of MAFbx/atrogin1 may suggest onset of 52 degenerative changes in VL muscle integrity of obese rats. DIO-R animals exhibited fewer 53 inflammatory changes compared to DIO-P animals, suggesting a protective effect of obesity 54 resistance on local inflammation.