Jean-Aimé Simoneau

Subcutaneous Abdominal Fat and Thigh Muscle Composition Predict Insulin Sensitivity Independently of Visceral Fat

Whether visceral adipose tissue has a uniquely powerful association with insulin resistance or whether subcutaneous abdominal fat shares this link has generated controversy in the area of body composition and insulin sensitivity. An additional issue is the potential role of fat deposition within skeletal muscle and the relationship with insulin resistance. To address these matters, the current study was undertaken to measure body composition, aerobic fitness, and insulin sensitivity within a cohort of sedentary healthy men (n = 26) and women (n = 28). The subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m2), underwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mass (FFM) and fat mass (FM), computed tomography to measure cross-sectional abdominal subcutaneous and visceral adipose tissue, and computed tomography (CT) of mid-thigh to measure muscle cross-sectional area, muscle attenuation, and subcutaneous fat. Insulin sensitivity was measured using the glucose clamp technique (40 mU · m∼2 · min−1), in conjunction with [3-3H]glucose isotope dilution. Maximal aerobic power (Vo2max) was determined using an incremental cycling test. Insulin-stimulated glucose disposal (Rd) ranged from 3.03 to 16.83 mg · min−1· kg−1 FFM. Rd was negatively correlated with FM (r = -0.58), visceral fat (r = -0.52), subcutaneous abdominal fat (r = -0.61), and thigh fat (r = -0.38) and positively correlated with muscle attenuation (r = 0.48) and Vo2max (r = 0.26, P < 0.05). In addition to manifesting the strongest simple correlation with insulin sensitivity, in stepwise multiple regression, subcutaneous abdominal fat retained significance after adjusting for visceral fat, while the converse was not found. Muscle attenuation contributed independent significance to multiple regression models of body composition and insulin sensitivity, and in analysis of obese subjects, muscle attenuation was the strongest single correlate of insulin resistance. In summary, as a component of central adiposity, subcutaneous abdominal fat has as strong an association with insulin resistance as visceral fat, and altered muscle composition, suggestive of increased fat content, is an important independent marker of insulin resistance in obesity.

Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss

The current study was undertaken to investigate fatty acid metabolism by skeletal muscle to examine potential mechanisms that could lead to increased muscle triglyceride in obesity. Sixteen lean and 40 obese research volunteers had leg balance measurement of glucose and free fatty acid (FFA) uptake (fractional extraction of [9,103H]oleate) and indirect calorimetry across the leg to determine substrate oxidation during fasting and insulin-stimulated conditions. Muscle obtained by percutaneous biopsy had lower carnitine palmitoyl transferase (CPT) activity and oxidative enzyme activity in obesity ( P < 0.05). During fasting conditions, obese subjects had an elevated leg respiratory quotient (RQ, 0.83 ± 0.02 vs. 0.90 ± 0.01; P < 0.01) and reduced fat oxidation but similar FFA uptake across the leg. During insulin infusions, fat oxidation by leg tissues was suppressed in lean but not obese subjects; rates of FFA uptake were similar. Fasting values for leg RQ correlated with insulin sensitivity ( r = -0.57, P < 0.001). Thirty-two of the obese subjects were restudied after weight loss (WL, -14.0 ± 0.9 kg); insulin sensitivity and insulin suppression of fat oxidation improved ( P < 0.01), but fasting leg RQ (0.90 ± 0.02 vs. 0.90 ± 0.02, pre-WL vs. post-WL) and muscle CPT activity did not change. The findings suggest that triglyceride accumulation in skeletal muscle in obesity derives from reduced capacity for fat oxidation and that inflexibility in regulating fat oxidation, more than fatty acid uptake, is related to insulin resistance.The current study was undertaken to investigate fatty acid metabolism by skeletal muscle to examine potential mechanisms that could lead to increased muscle triglyceride in obesity. Sixteen lean and 40 obese research volunteers had leg balance measurement of glucose and free fatty acid (FFA) uptake (fractional extraction of [9,10 (3)H]oleate) and indirect calorimetry across the leg to determine substrate oxidation during fasting and insulin-stimulated conditions. Muscle obtained by percutaneous biopsy had lower carnitine palmitoyl transferase (CPT) activity and oxidative enzyme activity in obesity (P < 0.05). During fasting conditions, obese subjects had an elevated leg respiratory quotient (RQ, 0.83 +/- 0.02 vs. 0.90 +/- 0.01; P < 0.01) and reduced fat oxidation but similar FFA uptake across the leg. During insulin infusions, fat oxidation by leg tissues was suppressed in lean but not obese subjects; rates of FFA uptake were similar. Fasting values for leg RQ correlated with insulin sensitivity (r = -0.57, P < 0.001). Thirty-two of the obese subjects were restudied after weight loss (WL, -14.0 +/- 0.9 kg); insulin sensitivity and insulin suppression of fat oxidation improved (P < 0.01), but fasting leg RQ (0.90 +/- 0.02 vs. 0.90 +/- 0.02, pre-WL vs. post-WL) and muscle CPT activity did not change. The findings suggest that triglyceride accumulation in skeletal muscle in obesity derives from reduced capacity for fat oxidation and that inflexibility in regulating fat oxidation, more than fatty acid uptake, is related to insulin resistance.

Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss

A number of biochemical defects have been identified in glucose metabolism within skeletal muscle in obesity, and positive effects of weight loss on insulin resistance are also well established. Less is known about the capacity of skeletal muscle for the metabolism of fatty acids in obesity‐related insulin resistance and of the effects of weight loss, though it is evident that muscle contains increased triglyceride. The current study was therefore undertaken to profile markers of human skeletal muscle for fatty acid metabolism in relation to obesity, in relation to the phenotype of insulin‐resistant glucose metabolism, and to examine the effects of weight loss. Fifty‐five men and women, lean and obese, with normal glucose tolerance underwent percutaneous biopsy of vastus lateralis skeletal muscle for determination of HADH, CPT, heparin‐releasable (Hr) and tissue‐extractable (Ext) LPL, CS, COX, PFK, and GAPDH enzyme activities, and content of cytosolic and plasma membrane FABP. Insulin sensitivity was measured using the euglycemic clamp method. DEXA was used to measure FM and FFM. In skeletal muscle of obese individuals, CPT, CS, and COX activities were lower while, conversely, they had a higher or similar content of FABPC and FABPPM than in lean individuals. Hr and Ext LPL activities were similar in both groups. In multivariate and simple regression analyses, there were significant correlations between insulin resistance and several markers of FA metabolism, notably, CPT and FABPPM. These data suggest that in obesity‐related insulin resistance, the metabolic capacity of skeletal muscle appears to be organized toward fat esterification rather than oxidation and that dietary‐induced weight loss does not correct this disposition.—Simoneau, J.‐A., Veerkamp, J. H., Turcotte, L. P., Kelley, D. E. Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J. 13, 2051–2060 (1999)

Impact of exercise intensity on body fatness and skeletal muscle metabolism.

The impact of two different modes of training on body fatness and skeletal muscle metabolism was investigated in young adults who were subjected to either a 20-week endurance-training (ET) program (eight men and nine women) or a 15-week high-intensity intermittent-training (HIIT) program (five men and five women). The mean estimated total energy cost of the ET program was 120.4 MJ, whereas the corresponding value for the HIIT program was 57.9 MJ. Despite its lower energy cost, the HIIT program induced a more pronounced reduction in subcutaneous adiposity compared with the ET program. When corrected for the energy cost of training, the decrease in the sum of six subcutaneous skinfolds induced by the HIIT program was ninefold greater than by the ET program. Muscle biopsies obtained in the vastus lateralis before and after training showed that both training programs increased similarly the level of the citric acid cycle enzymatic marker. On the other hand, the activity of muscle glycolytic enzymes was increased by the HIIT program, whereas a decrease was observed following the ET program. The enhancing effect of training on muscle 3-hydroxyacyl coenzyme A dehydrogenase (HADH) enzyme activity, a marker of the activity of beta-oxidation, was significantly greater after the HIIT program. In conclusion, these results reinforce the notion that for a given level of energy expenditure, vigorous exercise favors negative energy and lipid balance to a greater extent than exercise of low to moderate intensity. Moreover, the metabolic adaptations taking place in the skeletal muscle in response to the HIIT program appear to favor the process of lipid oxidation.

Genetic determinism of fiber type proportion in human skeletal muscle.

Skeletal muscle fiber type distribution is quite heterogeneous, with about 25% of North American Caucasian men and women having either less than 35% or more than 65% of type I fiber in their vastus lateralis muscle. To what extent human skeletal muscle fiber type proportion is under the control of genetic factors is examined in this paper. The results summarized here suggest that about 15% of the total variance in the proportion of type I muscle fibers in human is explained by the error component related to muscle sampling and technical variance, that about 40% of the phenotype variance is influenced by environmental factors, and the remaining variance (about 45%) is associated with inherited factors. These estimates suggest that a difference of about 30% in type I fibers among individuals could be explained exclusively by differences in the local environment and level of muscular contractile activity. However, unidentified genetic factors would have to be invoked to account for the observation that the skeletal muscle of about 25% of the North American Caucasian population have either less than 35% or more than 65% of type I fibers.—Simoneau, J.‐A., Bouchard, C. Genetic determinism of fiber type pro‐portion in human skeletal muscle. FASEB J. 9, 1091‐1095 (1995)

Fat content in individual muscle fibers of lean and obese subjects

OBJECTIVE: To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity.DESIGN: Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals.SUBJECTS: Seven lean controls (body mass index (BMI) 23.0±3.3 kg/m2; mean±s.d.) and 14 obese (BMI 33.7±2.7 kg/m2) individuals; both groups included comparable proportions of men and women.MEASUREMENTS: Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined.RESULTS: The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298±135 vs 129±75; obese vs lean, P<0.05), IIA (132±67 vs 79±29; P<0.05), and IIB (103±63 vs 51±13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2±5.7 vs 19.7±6.4%; P<0.05).CONCLUSION: The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

Human skeletal muscle fiber type alteration with high-intensity intermittent training

SummaryThe response of muscle fiber type proportions and fiber areas to 15 weeks of strenuous high-intensity intermittent training was investigated in twenty-four carefully ascertained sedentary (14 women and 10 men) and 10 control (4 women and 6 men) subjects. The supervised training program consisted mainly of series of supramaximal exercise lasting 15 s to 90 s on a cycle ergometer. Proportions of muscle fiber type and areas of the fibers were determined from a biopsy of the vastus lateralis before and after the training program. No significant change was observed for any of the histochemical charactertics in the control group. Training significantly increased the proportion of type I and decreased type IIb fibers, the proportion of type IIa remained unchanged. Areas of type I and IIb fibers increased significantly with training. These results suggest that high-intensity intermittent training in humans may alter the proportion of type I and the area of type I and IIb fibers and in consequence that fiber type composition in human vastus lateralis muscle is not determined solely by genetic factors.

Species-specific effects of chronic nerve stimulation upon tibialis anterior muscle in mouse, rat, guinea pig, and rabbit

Tibialis anterior (TA) muscle of mouse, rat, guinea pig, and rabbit was indirectly stimulated for 10 h/day at 10 Hz up to 28 days. Changes in the activity levels of hexokinase (HK), phosphofructokinase (PFK) glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), creatine kinase (CK), citrate synthase (CS), malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HADH), and β-hydroxybutyrate dehydrogenase (HBDH) were compared. Although the direction of changes in the enzyme activity pattern was in accordance with previous findings on rabbit TA, the magnitude of the responses varied markedly between themammals under study. Mouse TA was almost unaffected. A major effect of chronic stimulation in rat, guinea pig and rabbit was an increase in enzyme activities of aerobic-oxidative metabolism. According to intrinsic differences of the muscles under study, the increases varied among the species and appeared to be inversely related to the basal levels of these enzymes in the unstimulated muscles. Conversely, glycolytic enzyme activities (PFK, GAPDH, LDH) markedly decreased in rat, guinea pig, and rabbit, and were only slightly reduced in mouse. Changes in HK and HBDH activities displayed the largest variations in the induced change between species. These results indicate species-specific patterns of metabolic adaptation to increased contractile activity.

Familial Resemblance in Maximal Heart Rate, Blood Lactate and Aerobic Power

There are considerable interindividual differences in maximal oxygen uptake per kilogram of body weight (VO2 max/kg), maximal heart rate (max HR) and maximal blood lactate (max blood La) measured during a progressive exercise test. The aim of the study was to quantify the familial relationships for these variables. Parents and children of 38 families of French-Canadian descent were submitted to a modified Balke treadmill test. VO2 max/kg and max HR were the highest values reached during the test for 1 min. Max blood La was obtained from a blood sample taken 2 min after the test. The effects of age and sex were significant for max blood La and VO2 max/kg in each generation. Scores were thus adjusted through multiple regression procedures (age + sex + age X sex + age2), yielding residuals which were submitted to further analysis. Intraclass correlations (ri) were significant in pairs of sibs for max blood La and max HR, i.e. 0.28 (p less than 0.01) and 0.43 (p less than 0.05), respectively. For VO2 max/kg, pairs of spouses and sibs were about similarly correlated (ri = 0.20 and 0.15; p less than 0.05). Data suggested that children were more related to their mother than to their father for VO2 max/kg, VO2 max/kg of fat-free weight, and particularly for max HR. It was concluded that familial resemblance and heritability estimates for maximal aerobic power, max HR and max blood La were quite low and generally nonsignificant. Correlations between biological sibs were, however, consistently significant for max HR and max blood La. The suggestion of a maternal effect in maximal aerobic power should be further investigated.

Muscle fiber types of women after resistance training - quantitative ultrastructure and enzyme activity

Muscle biopsies of the vastus lateralis muscle taken before and after 18 weeks of resistance training were compared by preparing frozen cross sections for electron microscopy and using adjacent sections for fiber typing by myosin ATPase activity. Quantitative ultrastructural changes were observed in histochemically-identified muscle fiber types of twelve young women who underwent the training. The percentage of type IIB fibers decreased and IIA fibers increased. The cross-sectional area of all major fiber types increased with training. The absolute volume of myofibrils, intermyofibrillar space, and mitochondria increased with training for most major fiber types (type I, IIA and IIAB), but the relative volume percentages were not significantly changed because of corresponding fiber hypertrophy. Mean mitochondrial size for types I and IIA and myofibril size for types IIC and IIB increased significantly with training. The capillary number per fiber and density did not change with training. Activity levels were measured for selected glycolytic and oxidative enzymes. Cytochrome oxidase and hexokinase increased significantly with training, while creatine kinase, citrate synthase, phosphofructokinase, glyceraldehyde phosphate dehydrogenase and hydroxyacyl CoA dehydrogenase enzymes were not significantly altered. The results suggest that this type of high-repetition resistance training causes the intracellular components of all fiber types to increase proportionally with an increase in fiber size. In addition, the enzyme analysis indicates the muscle as a whole may increase its oxidative phosphorylation capacity in conjunction with the decreased percentage of type IIB fibers.