Context: Intramuscular lipid content increases with aging and obesity, and is directly related to impaired glucose tolerance and insulin resistance.

Objective: Our purpose was to determine the effects of aerobic exercise training (AEX) with and without weight loss (WL) on mid-thigh low-density muscle (LDM: a measure of intramuscular lipid), and whether changes in LDM impact glucose tolerance in sedentary older men.

Design: Forty-six men (60.4 ± 1.1 years) completed six months of AEX (n=34) or AEX+WL (n=12) and had oral glucose tolerance tests (OGTT) and computed tomography measures of LDM and regional abdominal and thigh fat depot areas.

Results: At baseline, LDM area directly correlated with fasting plasma glucose (FPG), 120-min glucose (G₁₂₀), and glucose area under the curve (G_AUC) during an OGTT (r = 0.44, r = 0.51, and r = 0.54, respectively, p<0.01). After the interventions, the AEX+WL group had greater decreases in LDM (-13.5% vs. +1.3%, respectively), FPG (-8.3% vs. +2.1%, respectively), G₁₂₀ (-22.5% vs. -3.6%, respectively), and G_AUC (-17.3% vs. -3.1%, respectively) than the AEX group. In the entire sample, the decreases in LDM correlated with reductions in FPG, G₁₂₀, and G_AUC during an OGTT (r = 0.31, r = 0.34, and r = 0.41, p<0.05). Changes in other regional fat depots did not independently correlate with glucose tolerance or insulin responses.

Conclusion: AEX+WL is more efficacious than AEX for reducing LDM and glucose tolerance. The improvement in glucose tolerance may be partially mediated by decreases in LDM in older men.