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Background: Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals., Methods: Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions., Results: Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin., Conclusion: Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine effects of physical activity (PA) with diet-induced weight loss on energy metabolism in adults with severe obesity., Methods: Adults with severe obesity (n = 11) were studied across 6 months of intervention, then compared with controls with less severe obesity (n = 7) or normal weight (n = 9). Indirect calorimetry measured energy metabolism during exercise and rest. Markers of muscle oxidation were determined by immunohistochemistry. Data were presented as medians., Results: The intervention induced 7% weight loss (P = 0.001) and increased vigorous PA by 24 min/wk (P = 0.02). During exercise, energy expenditure decreased, efficiency increased (P ≤ 0.03), and fatty acid oxidation (FAO) did not change. Succinate dehydrogenase increased (P = 0.001), but fiber type remained the same. Post-intervention subjects' resting metabolism remained similar to controls. Efficiency was lower in post-intervention subjects compared with normal-weight controls exercising at 25 W (P ≤ 0.002) and compared with all controls exercising at 60% VO2peak (P ≤ 0.019). Resting and exercise FAO of post-intervention subjects remained similar to adults with less severe obesity. Succinate dehydrogenase and fiber type were similar across all body weight statuses., Conclusions: While metabolic adaptations to PA during weight loss occur in adults with severe obesity, FAO does not change. Resulting FAO during rest and exercise remains similar to adults with less severe obesity., (© 2016 The Obesity Society.)

Both Roux-en-Y gastric bypass (RYGB) surgery and exercise can improve insulin sensitivity in individuals with severe obesity. However, the impact of RYGB with or without exercise on skeletal muscle mitochondria, intramyocellular lipids, and insulin sensitivity index (SI) is unknown. We conducted a randomized exercise trial in patients (n = 101) who underwent RYGB surgery and completed either a 6-month moderate exercise (EX) or a health education control (CON) intervention. SI was determined by intravenous glucose tolerance test. Mitochondrial respiration and intramyocellular triglyceride, sphingolipid, and diacylglycerol content were measured in vastus lateralis biopsy specimens. We found that EX provided additional improvements in SI and that only EX improved cardiorespiratory fitness, mitochondrial respiration and enzyme activities, and cardiolipin profile with no change in mitochondrial content. Muscle triglycerides were reduced in type I fibers in CON, and sphingolipids decreased in both groups, with EX showing a further reduction in a number of ceramide species. In conclusion, exercise superimposed on bariatric surgery-induced weight loss enhances mitochondrial respiration, induces cardiolipin remodeling, reduces specific sphingolipids, and provides additional improvements in insulin sensitivity., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Aging is associated with a loss of muscle mass and increased body fat. The effects of diet-induced weight loss on muscle mass in older adults are not clear., Purpose: This study examined the effects of diet-induced weight loss, alone and in combination with moderate aerobic exercise, on skeletal muscle mass in older adults., Methods: Twenty-nine overweight to obese (body mass index = 31.8 +/- 3.3 kg/m(2)) older (67.2 +/- 4.2 years) men (n = 13) and women (n = 16) completed a 4-month intervention consisting of diet-induced weight loss alone (WL; n = 11) or with exercise (WL/EX; n = 18). The WL intervention consisted of a low-fat, 500-1,000 kcal/d caloric restriction. The WL/EX intervention included the WL intervention with the addition of aerobic exercise, moderate-intensity walking, three to five times per week for 35-45 minutes per session. Whole-body dual-energy x-ray absorptiometry, thigh computed tomography (CT), and percutaneous muscle biopsy were performed to assess changes in skeletal muscle mass at the whole-body, regional, and cellular level, respectively., Results: Mixed analysis of variance demonstrated that both groups had similar decreases in bodyweight (WL, -9.2% +/- 1.0%; WL/EX, -9.1% +/- 1.0%) and whole-body fat mass (WL, -16.5%, WL/EX, -20.7%). However, whole-body fat-free mass decreased significantly (p < .05) in WL (-4.3% +/- 1.2%) but not in WL/EX (-1.1% +/- 1.0%). Thigh muscle cross-sectional area by CT decreased in both groups (WL, -5.2% +/- 1.1%; WL/EX, -3.0% +/- 1.0%) and was not statistically different between groups. Type I muscle fiber area decreased in WL (-19.2% +/- 7.9%, p = .01) but remained unchanged in WL/EX (3.4% +/- 7.5%). Similar patterns were observed in type II fibers (WL, -16.6% +/- 4.0%; WL/EX, -0.2% +/- 6.5%)., Conclusion: Diet-induced weight loss significantly decreased muscle mass in older adults. However, the addition of moderate aerobic exercise to intentional weight loss attenuated the loss of muscle mass.

Background: Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults.Methods: Physically inactive older (68.6 ± 4.5 years) obese (body mass index 37.4 ± 4.9 kg/m2) adults were randomized to health education control (HEC; n = 25); diet-induced weight loss (WL; n = 31); or weight loss and exercise (WLEX; n = 28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, body composition by dual-energy X-ray absorptiometry and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test.Results: WLEX improved (p < .05) peripheral insulin sensitivity (+75 ± 103%) versus HEC (+12 ± 67%); WL (+36 ± 47%) versus HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) versus WL (-2 ± 24%) and prevented reductions in strength and lean mass induced by WL (p < .05). WLEX decreased abdominal adipose tissue (-16 ± 9%) versus HEC (-3 ± 8%) and intermuscular adipose tissue (-15 ± 13%) versus both HEC (+9 ± 15%) and WL (+2 ± 11%; p < .01).Conclusions: Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals.Methods: Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions.Results: Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin.Conclusion: Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults. [ABSTRACT FROM AUTHOR]

Weight loss and exercise-induced improvements in insulin resistance OR) am variable; some individuals experience robust enhancements in insulin sensitivity, while others do not. Thyroid hormone status is related to IR, but it is not clear whether subclinical hypothyroidism may help to explain the variability in improvements in IR. The purpose of this study was to examine the association between thyroid hormone status and the improvement in IR following exercise training in impaired glucose tolerant (IGT) subjects. Ten overweight to obese (BMI= 32 ±2.8 kg/m²) older (age=66.5±4.4 years) subjects completed a 16-week program consisting of 3-5 days per week, 30-45 min per session of moderate aerobic exercise (mostly walking). Insulin sensitivity, determined by a euglycemic hyperinsulinemic clamp, was measured before and after the intervention. A retrospective nested case control analysis was performed in subclinical hypothyroid (hypothyroid; N=5, TSH 4.38 ± 1.09 uIU/ml) versus normal thyroid (enthyroid; N=5, TSH 1.93 ±32 uIU/ml) subjects, matched on gender (3 women and 2 men in each group) and BMI. A 2x2 mixed ANOVA was performed on insuli a significant amount of body weight (∼6%, P≤0.001). These data suggest that despite a similar exercise program and weight loss, subclinical hypothyroidism may interfere with beneficial adaptations on muscle metabolism that typically occur with lifestyle modification. Further studies are needed to explore potential mechanisms that may underlie this blunted response in hypothyroid patients. ADA-Funded Research [ABSTRACT FROM AUTHOR]

Lifestyle modification, including a combination of weight loss and exercise, is especially effective in reducing the incidence of type 2 diabetes (T2DM) in older, high-risk individuals. However, the effects of exercise and diet-induced weight loss on insulin resistance and other cardiometabolic risk factors in older adults are not clear. The purpose of this study was to examine effects of weight loss and exercise, either alone or in combination, on insulin sensitivity and other cardiometabolic risk factors. Twenty-nine overweight/obese (BMI 31.8±3.2 kg⋅m[sup -2]) older (67.6±4.1 years) men (N=1 5) and women (N=14) with impaired glucose tolerance or newly diagnosed, drug-naïve T2DM were randomly assigned to one of the three lifestyle interventions: diet-induced weight loss (WL, N=9), exercise (EX, N=6) or combined weight loss and exercise (WL+EX, N=14). Insulin sensitivity, determined using a hyperinsulinemic (40 mU⋅m[sup -2]⋅min[sup -1]) euglycemic clamp, was improved (P<0.05) by each intervention: WL (23%), EX (26%) and WL+EX (31%). Fat mass, determined by DEXA, was decreased (P<0.05) following each intervention: WL (-18%), EX (-6%) and WL+EX (-19%). While no changes were observed in serum cholesterol or triglycerides, both systolic (WL -12%, EX -12% and WL+EX -11%) and diastolic (WL -8%, EX - 13%, and WL+EX -15%) were decreased (P<0.05) following intervention. C-reactive protein was decreased in WL (-28%) and WL+EX (-41%), but increased in EX (13%), all P<0.05. Changes in physical fitness (VO[sub 2max]) better predicted (r²=0.23, P<0.05) changes in insulin sensitivity than changes in fat-mass (r²=0.03, P=ns). In conclusion, diet-induced weight loss and exercise training independently, but not additively, improve insulin resistance, hypertension and inflammatory status in older adults with or at risk for developing T2DM. Additionally, enhanced aerobic fitness is a better predictor of improved insulin action than are changes in overall fat mass. ADA-Funded Research [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the hypothesis that subclinical hypothyroidism may undermine the beneficial adaptations to lifestyle modifications, blunting the improvement of insulin sensitivity by exercise training and weight loss. Several subclinical hypothyroid subjects and matched euthyroid control subjects underwent a euglycemic hyperinsulinemic clamp and peak oxygen uptake test, before and after a program of moderate aerobic exercise. The researchers found that subclinical hypothyroidism may interfere with beneficial adaptations on muscle metabolism and physical fitness that typically occur with weight loss and increased physical activity.

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 (VO2 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⁻¹/μU/ml, P = 0.019) above that of surgery. Exercise also improved S(G) (ITT: CON vs. EX; +0.0023 vs. +0.0063 min⁻¹, P = 0.009) compared with the CON group. Exercise improved cardiorespiratory fitness (VO2 peak) compared with the CON group. Conclusion: Moderate exercise following RYGB surgery provides additional improvements in S(I), S(G), and cardiorespiratory fitness compared with a sedentary lifestyle during similar weight loss. Trial Registration: clinicaltrials.gov identifier: NCT00692367. Funding: This study was funded by the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK078192) and an NIH/National Center for Research Resources/Clinical and Translational Science Award (UL1 RR024153). [ABSTRACT FROM AUTHOR]