Skeletal muscle lipid metabolism with obesity

Hulver, Matthew W.; Berggren, Jason R.; Cortright, Ronald N.; Dudek, Ronald W.; Thompson, Rachel; Pories, Walter J.; MacDonald, Kenneth G.; Cline, Gary W.; Shulman, Gerald I.; Dohm, G. Lynis; Houmard, Joseph A.

doi:10.1152/ajpendo.00514.2002

Cited by 287 publications

(273 citation statements)

References 41 publications

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“…It was recently reported that obese subjects are able to maintain normal IMCL stores in the presence of increased lipid oxidation [6]. The previously reported reduced fatty acid uptake and/or fat oxidation in muscle of abdominally obese subjects [1,2,28,29] may be a characteristic of the more obese subject [30], suggesting that IMCL accumulation may only occur in the presence of a reduced capacity to oxidise fat.…”

Section: Discussionmentioning

confidence: 98%

“…Based on these results, it can be estimated that with the present number of subjects, a difference in IMCL of at least 25% was required for detection using this method, indicating that we might have failed to identify slight differences between groups. As already indicated above, part of the discrepancy between different studies on obesity and IMCL accumulation in muscle may be related to differences in the type of muscle studied (with concomitant variation in lipolytic activity, muscle fibre type and glycolytic and oxidative enzyme capacity) [35], the degree of obesity [30] or body fat distribution [1].…”

Section: Discussionmentioning

confidence: 99%

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Impaired ?-adrenergically mediated lipolysis in skeletal muscle of obese subjects

et al. 2004

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Aims/hypothesis. The aim of this study was to investigate whether the β 2 -adrenergically mediated increase in interstitial glycerol concentrations (used as an indicator of local lipolysis) was impaired in the skeletal muscle (the gastrocnemius muscle) of obese subjects compared with in that of lean subjects, and whether any differences in muscle lipolysis were related to differences in intramyocellular muscle triglyceride content. Methods. A microdialysis experiment was performed in the gastrocnemius muscle of eight lean and eight obese men (body fat 22.1±1.6% vs 32.7±1.6% respectively). After determining baseline extracellular glycerol concentrations, the probe was perfused with increasing concentrations of the β 2 -agonist, salbutamol (doses of 1, 10 and 100 µmol/l for 45-min periods). Local blood flow was determined using the ethanol dilution technique. Intramyocellular lipid content was determined using 1 H-magnetic resonance spectroscopy.Results. Compared with that in lean subjects, the β 2 -adrenergically mediated increase in glycerol concentrations (absolute and percentage change) was blunted in obese subjects (at 100 µmol/l of salbutamol, percentage change 12.0±12% vs 48±12%, p<0.05). The decrease in ethanol out : in ratio was less pronounced in the obese individuals (p<0.05), indicating a diminished increase in local muscle blood flow. Intramyocellular lipid content was comparable in both groups. Conclusions/interpretation. The capacity to increase skeletal interstitial glycerol concentrations during direct β 2 -adrenergic stimulation is impaired in obese subjects with normal intramyocellular concentrations, suggesting that this may be an early event in the process of triglyceride accumulation.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Impaired ?-adrenergically mediated lipolysis in skeletal muscle of obese subjects

et al. 2004

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“…Following weight loss, they had BMIs in the class II obesity range (35-39.9 kg/m 2 ) ( Table 1). Since the metabolic characteristics of primary myotubes from extremely obese participants may differ from those of obese participants [47], the conclusions drawn from this study may be limited to the population studied. Another limitation was the varying duration of the participants' weight stability prior to biopsy.…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility to oxidative damage in post-diabetic human myotubes

et al. 2009

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Aims/hypothesis Obesity is an important risk factor for the development of type 2 diabetes, but not all obese individuals develop this complication. The clinical signs of type 2 diabetes can often be reversed with weight loss; however, it is unknown whether the skeletal muscle oxidative stress associated with type 2 diabetes remains after weight loss. We hypothesised that chronic exposure to high glucose and insulin would re-elicit impaired metabolism in primary myotubes from patients with a history of type 2 diabetes. Methods Obese participants with or without type 2 diabetes completed a standardised weight loss protocol, following which all participants were euglycaemic and had similar indices of insulin sensitivity. Satellite cells were isolated from muscle biopsies and differentiated under low or high glucose and insulin conditions (HGI).

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“…Investigations of the measurement of LCACoA in humans are scarce, but a recent study reported increased LCACoA content in skeletal muscle from overweight/obese and extremely obese individuals compared with normal weight subjects [31]. Furthermore, total LCACoA content has been reported to be a better correlate of insulin action than measurements of TG m [8].…”

Section: Discussionmentioning

confidence: 99%

Disassociation of muscle triglyceride content and insulin sensitivity after exercise training in patients with Type 2 diabetes

et al. 2004

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Aim/hypothesis. We determined the effect of exercise training on insulin sensitivity and muscle lipids (triglyceride [TG m ] and long-chain fatty acyl CoA [LCACoA] concentration) in patients with Type 2 diabetes. Methods. Seven patients with Type 2 diabetes and six healthy control subjects who were matched for age, BMI, % body fat and VO 2 peak participated in a 3 days per week training program for 8 weeks. Insulin sensitivity was determined pre-and post-training during a 120 min euglycaemic-hyperinsulinaemic clamp and muscle biopsies were obtained before and after each clamp. Oxidative enzyme activities [citrate synthase (CS), β-hydroxy-acyl-CoA (β-HAD)] and TG m were determined from basal muscle samples pre-and post training, while total LCACoA content was measured in samples obtained before and after insulinstimulation, pre-and post training. Results. The training-induced increase in VO 2 peak (~20%, p<0.01) was similar in both groups. Compared with control subjects, insulin sensitivity was lower in the diabetic patients before and after training (~60%; p<0.05), but was increased to the same extent in both groups with training (~30%; p<0.01). TG m was increased in patients with Type 2 diabetes (170%; p<0.05) before, but was normalized to levels observed in control subjects after training. Basal LCACoA content was similar between groups and was unaltered by training. Insulin-stimulation had no detectable effect on LCACoA content. CS and β-HAD activity were increased to the same extent in both groups in response to training (p<0.001). Conclusion/interpretation. We conclude that the enhanced insulin sensitivity observed after short-term exercise training was associated with a marked decrease in TG m content in patients with Type 2 diabetes. However, despite the normalization of TG m to levels observed in healthy individuals, insulin resistance was not completely reversed in the diabetic patients. Type 2 diabetes is characterized by skeletal muscle insulin resistance and impaired glucose metabolism. In addition to disturbances in glucose homeostasis, individuals with Type 2 diabetes have an impaired lipid metabolism, reflected by increased circulating free fatty acids [1], reduced rates of whole body fat oxidation [2] and excessive deposition of lipids in various tissues including skeletal muscle [3]. With regard to muscle lipid status, there is evidence in humans that increased trigacylglycerol (TG m ) concentration [3,4,5,6,7] and increased long-chain fatty acyl CoA (LCACoA) content are negatively associated with whole body insulin action [8]. Considering the rela-

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Skeletal muscle lipid metabolism with obesity

Cited by 287 publications

References 41 publications

Impaired ?-adrenergically mediated lipolysis in skeletal muscle of obese subjects

Impaired ?-adrenergically mediated lipolysis in skeletal muscle of obese subjects

Increased susceptibility to oxidative damage in post-diabetic human myotubes

Disassociation of muscle triglyceride content and insulin sensitivity after exercise training in patients with Type 2 diabetes

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