Effects of Weight Loss and Physical Activity on Muscle Lipid Content and Droplet Size

<jats:title>Abstract</jats:title><jats:p><jats:bold><jats:italic>Objectives</jats:italic></jats:bold>: To address the potential effects of weight loss and physical activity (WL + Ex) on intramyocellular lipid (IMCL) and lipid droplet size in overweight and obese previously sedentary individuals.</jats:p><jats:p><jats:bold><jats:italic>Research Methods and Procedures</jats:italic></jats:bold>: IMCL and lipid droplet size was determined in vastus lateralis, obtained by percutaneous biopsy, from 21 obese volunteers (9 men/12 women), using Oil Red O staining, along with succinate dehydrogenase histochemistry and mitochondrial immunohistochemistry as measures of skeletal muscle oxidative capacity. Insulin sensitivity (IS) was determined by glucose clamp.</jats:p><jats:p><jats:bold><jats:italic>Results</jats:italic></jats:bold>: A 4‐month WL + Ex intervention resulted in ∼10% WL and ∼15% increase in maximal oxygen uptake, leading to a 46% increase in IS (all <jats:italic>p</jats:italic> < 0.01). IMCL did not significantly change (<jats:italic>p</jats:italic> = 0.36). However, the size of lipid droplets decreased after WL + Ex (<jats:italic>p</jats:italic> < 0.01), and this decrease in lipid droplet size correlated with increased IS (<jats:italic>p</jats:italic> < 0.01) and the amount of physical activity (<jats:italic>p</jats:italic> < 0.05). Succinate dehydrogenase activity and mitochondrial labeling increased significantly (<jats:italic>p</jats:italic> < 0.01), without a significant shift in fiber type distribution.</jats:p><jats:p><jats:bold><jats:italic>Discussion</jats:italic></jats:bold>: In summary, IMCL does not decrease in response to WL + Ex in obese, previously sedentary individuals, yet the lipid within muscle is dispersed into smaller droplets. This change in the size of lipid droplets, likely coupled with a concomitant increase in oxidative enzyme capacity, is correlated to improved IS.</jats:p>