Introduction:

Increased accumulation of intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) due to positive energy balance is strongly associated with increased insulin resistance¹. Life style interventions like exercise and calorie restriction create a negative balance, resulting in increased mobilization of ectopic fat and improved insulin sensitivity². In this study, we investigate the interaction between high fat diet and high intensity exercise in modulating the body weight, IHL and IMCL in rats.

Methods:

All experimental procedures were in compliance and approved by the local institutional committee. Male wistar rats were divided into three groups: control on normal chow (n=5), high fat diet (n=5) (HFD) and high fat diet + exercise (n=5) (HFD-EX). Chronic exercise intervention was performed on the exercise groups using animal treadmill (Columbus-1055SRM-E54 Exer-3/6-Dual). Exercise protocol involved treadmill running at the rate of 18m/min for 30 minutes/day for 12 weeks. In vivo MRS experiments performed on 7 T Bruker ClinScan MRS System with motion compensation using a 72mm volume resonator for RF transmit and 20mm receive only coil. Longitudinal imaging measurements were performed prior to exercise intervention (baseline) and after 2, 4, 8, 10 and 12 weeks of exercise intervention. Localized PRESS experiments were performed on a voxel size of 64 mm³, with 64 averages, TR=4s, TE=13ms, 2048 complex points and spectral width of 3500 Hz. Similar experiments were performed on tibialis anterior compartment of skeletal muscle with 128 averages on a 27 mm³ voxel. IHL and IMCL concentrations were estimated using LC Model³. Oral glucose tolerance test was performed following a 12-hour fasting conditions⁴. Glucose and plasma insulin was measured from blood sampled at 0, 10, 20, 30, 60, 90 and 120 minutes intervals and was used to derive the Matsuda Index of insulin sensitivity⁵. The effect size of the interventions on all fat depots and metabolic assessments were evaluated using the Hedge’s g measure, with bias correction for the small sample size⁶. P-values < 0.01 was considered statistically significant.

Results:

Compared to the control group, HFD had a significant positive effect on the body weight, soleus muscle weight, SAT, VAT, IMCL, IHL, and leptin, and a significant negative effect on the Matsuda index, mimicking the effects of an obesogenic environment. The effect of HFD on triglycerides and cholesterol was not significant. Long term exercise (HFD-EX) was able to produce significant decline in the body weight, all the fat depots, triglycerides, leptin as well as a significant improvement in the Matsuda index when compared to the HFD group.

Discussion and Conclusions:

High fat diet increases the risk for insulin resistance and reduces mitochondrial oxidative capacity^{7, 8}. The HFD group showed increased fat accumulation in abdomen, liver and muscle along with insulin resistance. Incomplete fat oxidation with lipid oversupply can result in accumulation of lipid intermediaries which can interfere with the insulin signaling pathway⁹. After intense exercise training the HFD rats show reduction in all fat depots and improvement in insulin sensitivity. Our results show that chronic exercise intervention can counteract the detrimental effects of an obesogenic environment on pathogenic fat accumulation and insulin resistance.

Acknowledgements

No acknowledgement found.

References

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