Covington Jeffrey D, Johannsen Darcy L, Coen Paul M, Burk David H, Obanda Diana N, Ebenezer Philip J, Tam Charmaine S, Goodpaster Bret H, Ravussin Eric, Bajpeyi Sudip
Laboratory of Skeletal Muscle Physiology, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Obesity (Silver Spring). 2017 Dec;25(12):2079-2087. doi: 10.1002/oby.21980. Epub 2017 Oct 25.
Intramyocellular lipid (IMCL) is inversely related to insulin sensitivity in sedentary populations, yet no prospective studies in humans have examined IMCL accumulation with overfeeding.
Twenty-nine males were overfed a high-fat diet (140% caloric intake, 44% from fat) for 8 weeks. Measures of IMCL, whole-body fat oxidation from a 24-hour metabolic chamber, muscle protein extracts, and muscle ceramide measures were obtained before and after the intervention.
Eight weeks of overfeeding did not increase overall IMCL. The content of smaller lipid droplets peripherally located in the myofiber decreased, while increases in larger droplets correlated inversely with glucose disposal rate. Overfeeding resulted in inhibition of Akt activity, which correlated with the reductions in smaller, peripherally located lipid droplets and drastic increases in ceramide content. Additionally, peripherally located lipid droplets were associated with more efficient lipid oxidation. Finally, participants who maintained a greater number of smaller, peripherally located lipid droplets displayed a better resistance to weight gain with overfeeding.
These results show that lipid droplet size and location rather than mere IMCL content are important to understanding insulin sensitivity.
在久坐人群中，肌内脂质（IMCL）与胰岛素敏感性呈负相关，但尚无关于人类过度喂养时IMCL蓄积情况的前瞻性研究。
29名男性接受8周的高脂肪饮食过度喂养（热量摄入为正常的140%，44%来自脂肪）。在干预前后分别测量IMCL、通过24小时代谢室测得的全身脂肪氧化、肌肉蛋白提取物以及肌肉神经酰胺含量。
8周的过度喂养并未增加总体IMCL。位于肌纤维外周的较小脂滴含量减少，而较大脂滴的增加与葡萄糖处置率呈负相关。过度喂养导致Akt活性受到抑制，这与外周较小脂滴的减少以及神经酰胺含量的急剧增加相关。此外，外周脂滴与更有效的脂质氧化相关。最后，在过度喂养时，维持较多外周较小脂滴的参与者对体重增加具有更好的抵抗力。
这些结果表明，脂滴大小和位置而非单纯的IMCL含量对于理解胰岛素敏感性很重要。
