Simona Zarini, Karin Zemski Berry, Amanda Garfield, Emily Macias, Purevsuren Jambal, Sophia Bowen, Melanie G Cree, Janet K Snell-Bergeon, Chris Johnson, P Darrell Neufer, Ian Tamburini, Marcus Seldin, Bryan C Bergman
Subcellular accumulation of lipids is linked to insulin resistance, but changes in localization from weight loss or exercise training have not been thoroughly explored. We evaluated the independent effects of two insulin-sensitizing interventions, weight loss and exercise training, on lipid subcellular distribution in fractionated skeletal muscle, muscle mitochondrial function, and gene expression. Exercise training increased cytosolic storage of diacylglycerols and sphingolipids, and weight loss increased cytosolic sphingosine and decreased mitochondrial/endoplasmic reticulum triacylglycerol and diacylglycerol accumulation. Exercise training prevented the negative effects of mitochondrial lipids on mitochondrial function. Changes in specific subcellular lipid storage help explain muscle insulin sensitization following lifestyle interventions.