Physical activity enhances insulin action in obese/overweight individuals. However, the exercise prescription required for the optimal enhancement is not known. The purpose of this study was to test the hypothesis that exercise training consisting of vigorous-intensity activity would enhance insulin sensitivity more substantially than moderate-intensity activity. Sedentary, overweight/obese subjects (n = 154) were randomly assigned to either control or an exercise group for 6 mo: 1) low-volume/moderate-intensity group [ approximately 12 miles walking/wk at 40-55% peak O2 consumption (Vo2 peak)], 2) low-volume/high-intensity group ( approximately 12 miles jogging/wk at 65-80% Vo2 peak), and 3) high-volume/high-intensity group ( approximately 20 miles jogging/wk at 65-80% Vo2 peak). Training volume (miles/wk) was achieved by exercising approximately 115 min/wk (low-volume/high-intensity group) or approximately 170 min/wk (low-volume/moderate-intensity and high-volume/high-intensity groups). Insulin action was measured with an insulin sensitivity index (SI) from an intravenous glucose tolerance test. In the control group, there was a decrement (P < 0.05) in SI. In contrast, all the exercise groups significantly (P < 0.05) increased SI; the relative increment in the low-volume/moderate-intensity and high-volume/high-intensity groups ( approximately 85%) were greater than in the low-volume/high-intensity group ( approximately 40%). In conclusion, physical activity encompassing a wide range of intensity and volume minimizes the insulin resistance that develops with a sedentary lifestyle. However, an exercise prescription that incorporated approximately 170 min of exercise/wk improved insulin sensitivity more substantially than a program utilizing approximately 115 min of exercise/wk, regardless of exercise intensity and volume. Total exercise duration should thus be considered when designing training programs with the intent of improving insulin action.

; 10.1152/ajpendo.00416.2001.-The purpose of this study was to test the hypothesis that muscle fiber type is related to obesity. Fiber type was compared 1) in lean and obese women, 2) in Caucasian (C) and African-American (AA) women, and 3) in obese individuals who lost weight after gastric bypass surgery. When lean (body mass index 24.0 Ϯ 0.9 kg/m 2 , n ϭ 28) and obese (34.8 Ϯ 0.9 kg/m 2 , n ϭ 25) women were compared, there were significant (P Ͻ 0.05) differences in muscle fiber type. The obese women possessed fewer type I (41.5 Ϯ 1.8 vs. 54.6 Ϯ 1.8%) and more type IIb (25.1 Ϯ 1.5 vs. 14.4 Ϯ 1.5%) fibers than the lean women. When ethnicity was accounted for, the percentage of type IIb fibers in obese AA was significantly higher than in obese C (31.0 Ϯ 2.4% vs. 19.2 Ϯ 1.9%); fewer type I fibers were also found in obese AA (34.5 Ϯ 2.8% vs. 48.6 Ϯ 2.2%). These data are consistent with the higher incidence of obesity and greater weight gain reported in AA women. With weight loss intervention, there was a positive relationship (r ϭ 0.72, P Ͻ 0.005) between the percentage of excess weight loss and the percentage of type I fibers in morbidly obese patients. These findings indicate that there is a relationship between muscle fiber type and obesity. adiposity; African-American; insulin resistance; morbid obesity; skeletal muscle SKELETAL MUSCLE IS A HETEROGENEOUS organ consisting of different muscle fiber phenotypes. In human skeletal muscle, histochemical staining for pH-sensitive myosin ATPase activity has revealed two major classifications of fiber type, the type I and type II fibers (3,28,31). The fast-twitch, type II fibers can be broadly categorized into type IIa and type IIb fibers, although other subclasses exist (3,29,31). The type I, or slow-twitch, muscle fibers tend to be oxidative and vascularized, whereas the type IIb fibers (fast twitch) are glycolytic in nature (28, 31). The type I fibers are also insulin sensitive compared with type II muscle (8,13,17).In humans, there can be substantial heterogeneity of muscle fiber types within a given mixed muscle group. Simoneau and Bouchard (32) concluded that, in the vastus lateralis, Ն25% of the North American Caucasian population possessed either less than 35% or more than 65% type I fibers; a range of 13-98% type I fibers has been reported (31). Several factors may be linked with such variance. We have observed that obese individuals exhibit fewer type I and more type IIb muscle fibers than lean subjects (9). Other research has reported a negative relationship between adiposity and the relative percentage of type I muscle fibers (9, 21, 36) and an increased percentage of type IIb muscle fibers in patients with type 2 diabetes (9, 23), in their insulin-resistant offspring (27), and in obese subjects (18,19,21,23). Such findings make it tempting to speculate that there is a relationship between muscle fiber composition and obesity.The purpose of the current study was to test the hypothesis that muscle fiber type is related to obesity. We tested this hypothesis in...

OBJECTIVETo determine whether circulating metabolic intermediates are related to insulin resistance and β-cell dysfunction in individuals at risk for type 2 diabetes.RESEARCH DESIGN AND METHODSIn 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry–based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates.RESULTSThe 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (SI) (R2 = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R2 = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R2 = 0.39). Sex differences were found for metabolic predictors of SI and DI.CONCLUSIONSIn addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.

Adiponectin is an adipocytokine that is hypothesized to be involved in the regulation of insulin action. The purpose of the present investigation was to determine whether plasma adiponectin is altered in conjunction with enhanced insulin action with exercise training. An insulin sensitivity index (SI) and fasting levels of glucose, insulin, and adiponectin were assessed before and after 6 mo of exercise training (4 days/wk for ∼45 min at 65–80% peak O2 consumption) with no loss of body mass (PRE, 91.9 ± 3.8 kg vs. POST, 91.6 ± 3.9 kg) or fat mass (PRE, 26.5 ± 1.8 kg vs. POST, 26.7 ± 2.2 kg). Insulin action significantly ( P < 0.05) improved with exercise training (SI +98%); however, plasma adiponectin concentration did not change (PRE, 6.3 ± 1.5 μg/ml vs. POST, 6.6 ± 1.8 μg/ml). In contrast, in a separate group of subjects examined before and after weight loss, there was a substantial increase in adiponectin (+281%), which was accompanied by enhanced insulin action (SI, +432%). These data suggest that adiponectin is not a contributory factor to the exercise-related improvements in insulin sensitivity.

Although exercise improves individual risk factors for metabolic syndrome (MS), there is little research on the effect of exercise on MS as a whole. The objective of this study was to determine how much exercise is recommended to decrease the prevalence of MS. Of 334 subjects randomly assigned, 227 finished and 171 (80 women, 91 men) had complete data for all 5 Adult Treatment Panel III-defined MS risk factors and were included in this analysis. Subjects were randomly assigned to a 6-month control or 1 of 3 eight-month exercise training groups of (1) low amount/moderate intensity (equivalent to walking approximately 19 km/week), (2) low amount/vigorous intensity (equivalent to jogging approximately 19 km/week), or (3) high amount/vigorous intensity (equivalent to jogging approximately 32 km/week). The low-amount/moderate-intensity exercise prescription improved MS relative to inactive controls (p <0.05). However, the same amount of exercise at vigorous intensity was not significantly better than inactive controls, suggesting that lower-intensity exercise may be more effective in improving MS. The high-amount/vigorous-intensity group improved MS relative to controls (p <0.0001), the low-amount/vigorous-intensity group (p = 0.001), and the moderate-intensity group (p = 0.07), suggesting an exercise-dose effect. In conclusion, a modest amount of moderate-intensity exercise in the absence of dietary changes significantly improved MS and thus supported the recommendation that adults get 30 minutes of moderate-intensity exercise every day. A higher amount of vigorous exercise had greater and more widespread benefits. Finally, there was an indication that moderate-intensity may be better than vigorous-intensity exercise for improving MS.

nondiabetic patients following RYGB surgery are typically quite modest compared with the presurgery condition (3). Moreover, there appear to be 2 discrete periods of improvement. The first is immediately after surgery, at which time hepatic, but not peripheral, S I improves in response to acute energy restriction (4-6), while greater, protracted weight loss appears to be more strongly associated with improved peripheral S I (7,8). Even with significant weight loss 1 year following RYBG surgery, peripheral S I is still low compared with that of lean metabolically healthy individuals (3,5,6,9).Exercise is considered a cornerstone for obesity treatment, and while it is not generally viewed to cause substantial body weight reduction (10), it can potently improve peripheral S I and glucose control (11-13) and can reduce the risk of T2D and cardiovascular disease (14,15). There is general consensus that even a single session of moderate intensity exercise can induce an improvement in S I (16). There is also evidence that exercise can BACKGROUND. Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S I ) in obese patients. Regular exercise can also improve S I in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S I and other cardiometabolic factors. METHODS.We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1-3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included S I and glucose effectiveness (S G ), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO 2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week).RESULTS. 119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). S I improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min -1 /μU/ml, P = 0.18 for Δ, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive S I improvement (PP: CON vs. EX; +1.57 vs. +2.69 min

While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/ AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18 -70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130 -190 mg/dl or HDL cholesterol Յ40 mg/dl for men or Յ45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/ exercise, 8 -12 repetitions/set, 2) AT, which was equivalent to ϳ19.2 km/wk (12 miles/wk) at 75% peak O2 uptake, and 3) full AT ϩ full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P Ͻ 0.05). RT resulted in a decrease in subcutaneous abdominal fat (P Ͻ 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P Ͻ 0.05) and trended toward a greater reduction in liver fat score (P Ͻ 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode. aerobic training; liver fat; resistance training; weight lifting; homeostasis model assessment WHILE THE BENEFITS OF BEING physically active are clear, many unresolved issues surround the optimal exercise prescription for these benefits. Many organizations recommend both aerobic training (AT) and resistance training (RT) for all adults. However, these recommendations are mainly based on the evaluation of each modality separately, as few studies have investigated the effects of combined AT and RT regimens compared with each modality individually. Furthermore, adherence to exercise recommendations of physicians is notoriously poor, and many patients cite lack of time as a reason for noncompliance. Understanding the effects of AT and RT is of critical importance if we are to apply evidence-based approaches to exercise recommendations to a wide population.Visceral fat and liver fat are associated with type 2 diabetes, metaboli...

In humans, skeletal muscle is a major site of peroxisome proliferator-activated receptor-␣ (PPAR-␣) expression, but its function in this tissue is unclear. We investigated the role of hPPAR-␣ in regulating muscle lipid utilization by studying the effects of a highly selective PPAR-␣ agonist, GW7647, on [14 C]oleate metabolism and gene expression in primary human skeletal muscle cells. Robust induction of PPAR-␣ protein expression occurred during muscle cell differentiation and corresponded with differentiation-dependent increases in oleate oxidation. In mature myotubes, 48-h treatment with 10 -1,000 nmol/l GW7647 increased oleate oxidation dose-dependently, up to threefold. Additionally, GW7647 decreased oleate esterification into myotube triacylglycerol (TAG), up to 45%. This effect was not abolished by etomoxir, a potent inhibitor of ␤-oxidation, indicating that PPAR-␣-mediated TAG depletion does not depend on reciprocal changes in fatty acid catabolism. Consistent with its metabolic actions, GW7647 induced mRNA expression of mitochondrial enzymes that promote fatty acid catabolism; carnitine palmityltransferase 1 and malonyl-CoA decarboxylase increased ϳ2-fold, whereas pyruvate dehydrogenase kinase 4 increased 45-fold. Expression of several genes that regulate glycerolipid synthesis was not changed by GW7647 treatment, implicating involvement of other targets to explain the TAG-depleting effect of the compound. These results demonstrate a role for hPPAR-␣ in regulating muscle lipid homeostasis. Diabetes 51: 901-909, 2002