Evidence for a Major Role of Skeletal Muscle Lipolysis in the Regulation of Lipid Oxidation During Caloric Restriction In Vivo

Hagström-Toft, Eva; Thörne, A.; Reynisdottir, Signy; Moberg, Erik; Rössner, Stephan; Bolinder, Jan; Arner, Peter

doi:10.2337/diabetes.50.7.1604

Cited by 44 publications

(47 citation statements)

References 34 publications

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“…Furthermore, heterogeneity in adipose tissue [39] and skeletal muscle [16] lipolysis has been reported. In addition, skeletal muscle and adipose tissue lipolysis can respond differently to insulin [40][41][42][43], also in relation to the insulin level [44,45]. Taken together, these factors hamper a clear interpretation of palmitate release in the arm and leg of healthy individuals and diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

et al. 2005

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Aims/hypothesis: In order to test the hypothesis that disturbances in skeletal muscle fatty acid metabolism with type 2 diabetes are not equally present in the upper and lower limbs, we studied fatty acid kinetics simultaneously across the arm and leg of type 2 diabetic patients (n=6) and matched control subjects (n=7) for 5 h under baseline conditions and during a 4-h hyperinsulinaemiceuglycaemic clamp. Methods: Limb fatty acid kinetics was determined by means of continuous [U-13 C]palmitate infusion and measurement of arteriovenous differences. Results: The systemic palmitate rate of appearance was 3.6±0.4 and 2.7±0.3 μmol·kg lean body mass −1 ·min −1 and decreased during the clamp by 26% (p=0.04) and 43% (p<0.01) in the diabetic patients and in the control subjects respectively. At baseline, palmitate uptake across the arm was similar in the two groups, whereas leg palmitate uptake was lower than in the arm in the diabetic patients. During the clamp, palmitate uptake decreased in the arm (−48%, p=0.02) and the leg (−38%, p=0.04) of the control subjects, whereas it decreased in the arm (−30%, p=0.04) but not in the leg of the diabetic patients. Similarly, during the clamp palmitate release was substantially suppressed in the arm (−47%, p<0.01) and the leg of the control subjects (−45%, p<0.01), but only in the arm of the diabetic patients (−45%, p<0.01). Conclusions/interpretation: The present data indicate that type 2 diabetes is characterised by heterogeneity in the dysregulation of skeletal muscle fatty acid metabolism, with only the leg, but not the arm, showing an impairment of fatty acid kinetics at baseline and during a hyperinsulinaemic-euglycaemic clamp causing a physiological increase in insulin concentration.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

et al. 2005

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“…However, it has been shown in several studies that interstitial glycerol is regulated differently (by both insulin and β-adrenergic stimulation) in adipose tissue as compared with muscle in both lean and obese subjects [16,25]. In addition, inhibition of lipolysis in adipose tissue and skeletal muscle is mediated by separate and specific phosphodiesterase subtypes [26].…”

Section: Discussionmentioning

confidence: 99%

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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“…Height, weight and waist circumference were measured and a subcutaneous abdominal fat biopsy was obtained as described by Lofgren et al [20]. Subsequently, the patients were subjected to a hyperinsulinaemic-euglycaemic clamp as described by Hagstrom-Toft et al [21]. In brief, they were given a bolus dose of insulin intravenously (1.6 U/m 2 body surface area; Actrapid, Novo Nordisk, Copenhagen, Denmark) and then an insulin infusion was delivered intravenously (0.12 U/m 2 min) for 120 min.…”

Section: Individualsmentioning

confidence: 99%

Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity

et al. 2010

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Aims/hypothesis The aim of this study was to determine whether the mean size of fat cells in either visceral or subcutaneous adipose tissue has an impact on the metabolic and inflammatory profiles in morbid obesity. Methods In 80 morbidly obese women, mean visceral (omental) and subcutaneous fat cell sizes were related to in vivo markers of inflammation, glucose metabolism and lipid metabolism. Results Visceral, but not subcutaneous, adipocyte size was significantly associated with plasma apolipoprotein B, total cholesterol, LDL-cholesterol and triacylglycerols (p ranging from 0.002 to 0.015, partial r ranging from 0.3 to 0.4). Subcutaneous, but not visceral, adipocyte size was significantly associated with plasma insulin and glucose, insulininduced glucose disposal and insulin sensitivity (p ranging from 0.002 to 0.005, partial r ranging from −0.34 to 0.35). The associations were independent of age, BMI, body fat mass or body fat distribution. Adipose tissue hyperplasia (i.e. many small adipocytes) in both regions was significantly associated with better glucose, insulin and lipid profiles compared with adipose hypertrophy (i.e. few large adipocytes) in any or both regions (p ranging from <0.0001 to 0.04). Circulating inflammatory markers were not associated with fat cell size or corresponding gene expression in the fat cell regions examined. Conclusions/interpretation In morbidly obese women region-specific variations in mean adipocyte size are associated with metabolic complications but not systemic or adipose inflammation. Large fat cells in the visceral region are linked to dyslipidaemia, whereas large subcutaneous adipocytes are important for glucose and insulin abnormalities. Hyperplasia (many small adipocytes) in both adipose regions may be protective against lipid as well as glucose/insulin abnormalities in obesity.

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Evidence for a Major Role of Skeletal Muscle Lipolysis in the Regulation of Lipid Oxidation During Caloric Restriction In Vivo

Cited by 44 publications

References 34 publications

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

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

Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity

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