Enhanced glucose metabolism in cultured human skeletal muscle after Roux-en-Y gastric bypass surgery

Nascimento, Emmani B. M.; Riedl, Isabelle; Jiang, Lake Q.; Kulkarni, Sameer S.; Näslund, Erik; Krook, Anna

doi:10.1016/j.soard.2014.11.001

Cited by 10 publications

(8 citation statements)

References 45 publications

(54 reference statements)

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“…In the present study, we observed that the derangement in glucose partitioning in response to insulin stimulation was restored to the level of lean controls after RYGB surgery. Our findings are consistent with previous studies and expand the growing evidence that RYGB surgery can remodel the metabolic characteristics related to glucose metabolism in human skeletal muscle 10,11 . In relation to the whole-body metabolic improvements after RYGB surgery, it can be postulated that the reduced production of glycolytic products (e.g., lactate) may possibly lead to the decrease of supplying glyconeogenic substrates to the liver, hence reducing glyconeogenesis and re-establishing whole body glycemic control after RYGB surgery.…”

Section: Discussionsupporting

confidence: 93%

“…Specifically, whole body glycemic control is normalized as early as 1-week after surgery 6 , whereas insulinstimulated glucose oxidation and peripheral insulin sensitivity improve more slowly [4][5][6] . Although the metabolic alterations of glucose metabolism at various phases after RYGB surgery have been well studied [7][8][9] , the intrinsic (i.e., skeletal muscle-specific) changes in skeletal muscle, via studying primary skeletal muscle cells raised in culture, just been explored recently 10,11 . Hinkley et al, recently reported that insulin action was enhanced in primary skeletal muscle cells as early as 1-month and retained at chronic phase (7-months) after RYGB surgery 10 , suggesting intrinsic remodeling in skeletal muscle occurs following RYGB surgery.…”

Section: Introductionmentioning

confidence: 99%

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

Kugler

Gundersen

et al. 2019

Int J Obes

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Background/Objectives: Impaired insulin-mediated glucose partitioning is an intrinsic metabolic defect in skeletal muscle from severely obese humans (BMI ≥ 40 kg/m 2). Roux-en-Y gastric bypass (RYGB) surgery has been shown to improve glucose metabolism in severely obese humans. The purpose of the study was to determine the effects of RYGB surgery on glucose partitioning, mitochondrial network morphology, and markers of mitochondrial dynamics skeletal muscle from severely obese humans. Subject/Methods: Human skeletal muscle cells were isolated from muscle biopsies obtained from RYGB patients (BMI = 48.0 ± 2.1, n=7) prior to, 1-month and 7-months following surgery and lean control subjects (BMI = 22.4 ± 1.1, n=7). Complete glucose oxidation, non-oxidized glycolysis rates, mitochondrial respiratory capacity, mitochondrial network morphology and regulatory proteins of mitochondrial dynamics were determined in differentiated human myotubes. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Kugler

Gundersen

et al. 2019

Int J Obes

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“…Protein expression of IRS1 has previously been shown to be both increased [66] and decreased [67] in human skeletal muscle after exercise. We have recently shown enhanced tyrosine phosphorylation of IRS1, concomitant with increased glucose metabolism in cultured myotubes obtained from donors before and after gastric by-pass surgery [68]. Our study indicates that exercise-induced changes in promoter methylation may be retained in satellite cells and during transition of these precursor cells to myoblasts and finally to myotubes, however, at present we cannot explain a possible link between this and the metabolic changes observed.…”

Section: Discussionmentioning

confidence: 55%

Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism

et al. 2017

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Background and aimsPhysical activity has preventive as well as therapeutic benefits for overweight subjects. In this study we aimed to examine effects of in vivo exercise on in vitro metabolic adaptations by studying energy metabolism in cultured myotubes isolated from biopsies taken before and after 12 weeks of extensive endurance and strength training, from healthy sedentary normal weight and overweight men.MethodsHealthy sedentary men, aged 40–62 years, with normal weight (body mass index (BMI) < 25 kg/m2) or overweight (BMI ≥ 25 kg/m2) were included. Fatty acid and glucose metabolism were studied in myotubes using [14C]oleic acid and [14C]glucose, respectively. Gene and protein expressions, as well as DNA methylation were measured for selected genes.ResultsThe 12-week training intervention improved endurance, strength and insulin sensitivity in vivo, and reduced the participants’ body weight. Biopsy-derived cultured human myotubes after exercise showed increased total cellular oleic acid uptake (30%), oxidation (46%) and lipid accumulation (34%), as well as increased fractional glucose oxidation (14%) compared to cultures established prior to exercise. Most of these exercise-induced increases were significant in the overweight group, whereas the normal weight group showed no change in oleic acid or glucose metabolism.Conclusions12 weeks of combined endurance and strength training promoted increased lipid and glucose metabolism in biopsy-derived cultured human myotubes, showing that training in vivo are able to induce changes in human myotubes that are discernible in vitro.

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“…Fatty acid oxidation was measured as previously described ( Nascimento et al., 2015 ). Briefly, PHHs were incubated in media with radioactive 3 H-palmitate (PerkinElmer) and cold palmitate (25 μM) in low-glucose DMEM for 3 hr.…”

Section: Methodsmentioning

confidence: 99%

“…Glycogen synthesis was determined as described ( Nascimento et al., 2015 ). PHHs were serum starved in DMEM (low glucose) for 4 hr and stimulated with 120 nM insulin or vehicle control for 2 hr with addition of 14 C-glucose (PerkinElmer) for the final 90 min.…”

Section: Methodsmentioning

confidence: 99%

Human Carboxylesterase 2 Reverses Obesity-Induced Diacylglycerol Accumulation and Glucose Intolerance

et al. 2017

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SummarySerine hydrolases are a large family of multifunctional enzymes known to influence obesity. Here, we performed activity-based protein profiling to assess the functional level of serine hydrolases in liver biopsies from lean and obese humans in order to gain mechanistic insight into the pathophysiology of metabolic disease. We identified reduced hepatic activity of carboxylesterase 2 (CES2) and arylacetamide deacetylase (AADAC) in human obesity. In primary human hepatocytes, CES2 knockdown impaired glucose storage and lipid oxidation. In mice, obesity reduced CES2, whereas adenoviral delivery of human CES2 reversed hepatic steatosis, improved glucose tolerance, and decreased inflammation. Lipidomic analysis identified a network of CES2-regulated lipids altered in human and mouse obesity. CES2 possesses triglyceride and diacylglycerol lipase activities and displayed an inverse correlation with HOMA-IR and hepatic diacylglycerol concentrations in humans. Thus, decreased CES2 is a conserved feature of obesity and plays a causative role in the pathogenesis of obesity-related metabolic disturbances.

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Enhanced glucose metabolism in cultured human skeletal muscle after Roux-en-Y gastric bypass surgery

Cited by 10 publications

References 45 publications

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

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

Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism

Human Carboxylesterase 2 Reverses Obesity-Induced Diacylglycerol Accumulation and Glucose Intolerance

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