Independent, combined, and duration‐dependent effects of diet and exercise on WAT inflammation and metabolic disturbances in obese C57/BL6 mice

Abstract

White adipose tissue (WAT) inflammation causes insulin resistance (IR) and hepatic steatosis (HS). Exercise training (EX) may decrease inflammation in WAT thereby ameliorating these disturbances, even in the absence of fat loss.This study compared low‐fat diet (LFD) and EX on WAT inflammation, IR, and HS in obese mice.Mice (n=109) fed a 45% fat diet (HFD) for 6 wks were randomly assigned to EX (treadmill, 5d/wk; 40 min/d; 65%VO2max) or sedentary (SED) groups. Mice remained on HFD or switched to a 10% fat diet (LFD). After 6 or 12 wks, WAT and liver were weighed and relative fat (rFat) was calculated. HS was assessed by total liver TG, and IR by HOMA. Rt‐PCR was used to determine WAT gene expression (MCP‐1, F480, TNF‐α, IL1ra, leptin). Comparisons were made using 2‐way (EX, LFD, EXxLFD) ANOVA covarying for rFat.EX and LFD reduced rFat and leptin, which improved when combined. Improvements in IR and HS were explained by reduced rFat at 6 wks. By 12 wks, MCP‐1, F480, TNF‐α, and IL1ra were reduced by EX and LFD. Regression analyses revealed EX, rFat, and WAT inflammation predicted reductions in IR (R2=.75; p<0.01); rFat and LFD predicted improvements in HS (R2=.51; p<0.01). From 6 to 12 wks, EX attenuated increases in rFat, HS, and WAT inflammation, but LFD decreased IL1ra.Unique metabolic consequences of SED and HFD are evident long‐term, highlighting the importance of both EX and LFD in preventing obesity‐related metabolic disturbances.Grant Funding SourceNIH T32 DK59802