A High-Fat Diet Rich In Polyunsaturated Fatty Acids Downregulates Glut4, But Not Skeletal Muscle Glycogen.

Abstract

High fat diets (HFD) are linked to the development of obesity and type 2 diabetes (T2D), characterized by defects in glycogen storage and increased lipid accumulation in skeletal muscle. Replacement of saturated fatty acids in high fat diets, with unsaturated (mono- and poly-unsaturated) fatty acids has been shown to reduce risks for insulin resistance, obesity and T2D. PURPOSE: The purpose of this study was to determine the effects of HFD differing in fatty acid composition, on skeletal muscle glycogen, mitochondrial, GLUT4, and lipid contents. METHODS: Male Sprague Dawley rats were fed a Western-style (21% fat by weight; 41% total energy) HFD for 9 weeks to induce obesity and then were divided into one of three HFD groups for an additional 6 weeks; a control chow group followed a 15-week low fat diet. Animals consumed either a) low fat Chow diet (CD) (4.8 % fat; 0.74% saturated; 2% mono; 1.77% poly; n=6), b) mixed fat Western diet (WD) (21% fat; 9.76% saturated; 7.68% mono; 3.48% poly; n=6), c) HFD rich in monounsaturated fatty acids (MUFA) (21% fat; 2.82% saturated; 16.01% mono; 2.18% poly; n=6), d) HFD rich in polyunsaturated fatty acids (PUFA) (21% fat; 2% fat; 2.97% mono; 16% poly; n=7). After 15 weeks, glycogen (periodic acid-schiff staining) mitochondria, GLUT4, and lipid content were measured in extensor digitorum longus muscle using immunohistochemical staining techniques and quantified with imageJ software. RESULTS: Following the 6-week treatment period, body weight (g) in the WD group was significantly greater compared to MUFA (p=0.0006), PUFA (p=0.02), and CD (p<0.0001). Glycogen content was significantly greater (p=0.04) in animals fed a WD compared to CD. (AU±SEM; CD: 4.41±0.04; WD: 4.74±0.13; MUFA: 4.54±0.08; PUFA: 4.54±0.11; one-way ANOVA p=0.11). A HFD rich in PUFA resulted in impaired GLUT4 content (p=0.02) compared to a CD (AU±SEM; CD: 77.38±2.22; WD: 63.46±3.80; MUFA: 61.49±8.46; PUFA: 52.84±5.13; one-way ANOVA p=0.03). There were no significant effects on mitochondrial or lipid content. CONCLUSION: A high fat diet rich in polyunsaturated fatty acids results in significantly lower GLUT4 content without negatively impacting skeletal muscle glycogen storage in high fat diet induced obese rats. A high fat diet rich in saturated fat resulted in greater muscle glycogen content compared to low fat fed rats.