Obesity leads to impairments in the morphology and organization of human skeletal muscle lipid droplets and mitochondrial networks, which are resolved with gastric bypass surgery‐induced improvements in insulin sensitivity

Abstract

Morbid obesity leads to severe qualitative alterations of both skeletal muscle lipid stores and mitochondrial networks. The degree of structural improvements after gastric bypass surgery was proportional to the improvements in whole body insulin sensitivity, suggesting an association between these events.

Roux-en-Y gastric bypass surgery restores insulin-mediated glucose partitioning and mitochondrial dynamics in primary myotubes from severely obese humans

“…In the present study, myotubes derived from severely obese individuals after RYGB surgery exhibited more interconnected networks with less fragmented individual mitochondria. Our observation is in agreement with a previous study showing improved mitochondrial network morphology in skeletal muscle tissue after RYGB surgery 15 , but adds novel information that such remodeling of mitochondrial structure was "imprinted" in skeletal muscle cells after RYGB surgery. Given that systemic factors are eliminated in the human muscle cell culture system, our results indicate that the improvement in the mitochondrial network in skeletal muscle after RYGB surgery is likely due to the intrinsic remodeling of muscle cells.…”

“…The machinery of mitochondrial dynamics is finely regulated by mitochondrial fusion proteins; Mitofusin 1 (Mfn1), Mitofusin 2 (Mfn2), and Optic Atrophy 1 (Opa1) and fission proteins Dynamin-Related Protein 1 (Drp1) and Fission 1 (Fis1) 13 . There is emerging evidence that obesity impairs mitochondrial dynamics with upregulation of mitochondrial fission that lead to fragmented mitochondrial networks, mitochondrial dysfunction and impaired glucose oxidation [14][15][16][17] and weight loss surgery improves these defects in skeletal muscle 15,18 . In addition, the imbalance of mitochondrial dynamics towards fission has been linked to increased glycolysis 19 and impaired glucose oxidation 14 .…”

Adipose tissue—more than just fat

“…They were able to show that in addition to improved skeletal muscle mitochondrial volume, number and density, regular exercise training can promote a more fused, tubular network, which may contribute to insulin sensitivity and substrate utilization. Kristensen et al also showed that skeletal mitochondrial function and skeletal muscle lipid storage differ in their quality between lean and obese subjects. They demonstrate that alterations in the structure of muscle mitochondrial network and in the quality of skeletal muscle lipid droplets go along with gastric bypass surgery–induced weight loss and insulin resistance remission.…”

“…A number of articles addressing basic mechanisms related to obesity have recently appeared in Acta physiologica. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] One area of clinical relevance for obese patients is the immune system. Duan et al 20 recapitulate the connections between a high-fat diet and diseases.…”

Obesity, adipocytes and insulin resistance—Friends for life?

“…Growing insulin resistance in obesity often leads to diabetes type 2 and metabolic syndrome. The underlying mechanism of obesity‐induced skeletal muscle insulin resistance is still unclear, but there is growing evidence that mitochondria dynamics are involved during this process and insulin resistance may reflect mitochondrial defects . Kristensen et al propose a hypothetical model of the cellular processes.…”