Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P < 0.0001), decreased body weight (P < 0.0001) and fat mass (P < 0.001), while fat-free mass was not altered (P > 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.

These data suggest that exercise alone is an effective nonpharmacological treatment strategy for insulin resistance, metabolic syndrome, and cardiovascular disease risk factors in older obese adults.

Circulating adiponectin is reduced in disorders associated with insulin resistance. This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle. Impaired glucose-tolerant older (Ͼ60 yr) obese (BMI 30 -40 kg/m 2 ) men (n ϭ 7) and women (n ϭ 14) were randomly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric (ExHypo, ϳ500 kcal reduction, n ϭ 11) or eucaloric diet (ExEu, n ϭ 10). Insulin sensitivity was determined by the euglycemic (5.0 mM) hyperinsulinemic (40 mU ⅐ m Ϫ2 ⅐ min Ϫ1 ) clamp. Adiponectin multimers [high (HMW), middle (MMW), and low molecular weight (LMW)] were measured by nondenaturing Western blot analysis. Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy samples. Greater weight loss occurred in ExHypo compared with ExEu subjects (8.0 Ϯ 0.6 vs. 3.2 Ϯ 0.6%, P Ͻ 0.0001). Insulin sensitivity improved postintervention in both groups (ExHypo: 2.5 Ϯ 0.3 vs. 4.4 Ϯ 0.5 mg ⅐ kg FFM Ϫ1 ⅐ min Ϫ1 , and ExEu: 2.9 Ϯ 0.4 vs.Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW (P Ͻ 0.03). The adiponectin SA ratio (HMW/ total) was increased following both interventions (P Ͻ 0.05) and correlated with the percent change in insulin sensitivity (P Ͻ 0.03). Postintervention adiponectin receptor mRNA expression was also significantly increased (AdipoR1 P Ͻ 0.03, AdipoR2 P Ͻ 0.02). These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression. glucose intolerance; diabetes; obesity; aging; gene expression MORE THAN A DECADE AGO, a novel secretory protein was discovered (31) with homology to collagen, a complement factor subunit, and an obscure protein associated with animal hibernation. This protein subsequently became known as adiponectin (AdiopQ, ACDC, Acrp30, apM-1, APM1, GBP28). Adiponectin is secreted primarily from adipocytes and circulates almost exclusively as homomultimeric full-length glycoprotein complexes that determine its activity and influence over lipid and carbohydrate metabolism (28). Low plasma adiponectin levels have been implicated in the development of insulin resistance and associated disorders such as obesity (30), hyperlipidemia (11), and type 2 diabetes (19). Evidence linking adiponectin with insulin action stems from increased insulin sensitivity upon adiponectin administration, resulting in an increase in skeletal muscle glucose uptake and hepatic fatty acid oxidation (38), as well as reports that reduced adiponectin expression occurs in parallel with the onset of insulin resistance in obese humans, rodents, and monkeys (2,15,17).Likewise, increased physical activity, weight loss, and/or caloric restriction have been shown to successfully reduce insulin resistance (14,26,36). However, inconsistent fi...

Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention.

Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFA(ox)) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; -598 +/- 125 kcal/day, 66 +/- 1 yr, 32.8 +/- 1.8 kg/m(2)) or a eucaloric (n = 8; 67 +/- 2 yr, 35.3 +/- 2.1 kg/m(2)) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-(14)C]palmitate) were assessed throughout a 7-h, 40 mU x m(-2) x min(-1) hyperinsulinemic euglycemic clamp, during which insulin resistance was induced in the last 5 h by a sustained elevation in plasma FFA (intralipid/heparin infusion). Despite greater weight loss in the hypocaloric group (-7.7 +/- 0.5 vs. -3.3 +/- 0.7%, P < 0.001), FFA-induced peripheral insulin resistance was improved equally in both groups. However, circulating FFA concentrations (2,123 +/- 261 vs. 1,764 +/- 194 micromol/l, P < 0.05) and FFA turnover (3.20 +/- 0.58 vs. 2.19 +/- 0.58 micromol x kg FFM(-1) x min(-1), P < 0.01) during hyperlipemia were suppressed only in the hypocaloric group. In contrast, whole body FFA(ox) was improved in both groups at rest and during hyperlipemia. These changes were driven by increases in intracellular lipid-derived FFA(ox) (12.3 +/- 7.7 and 14.7 +/- 7.8%, P < 0.05). We conclude that the exercise-induced improvement in FFA-induced insulin resistance is independent of the magnitude of weight loss and FFA turnover, yet it is linked to increased intracellular FFA utilization.

The exercise-induced reduction of plasma visfatin is most likely the result of weight loss and body composition changes. The potential regulatory role of visfatin in mediating the pancreatic insulin response to oral glucose requires further investigation.

Basal fat oxidation decreases with age. In obesity it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure (REE), basal substrate oxidation, and maximal oxygen consumption (VO 2 max) were measured in ten older (age 60 ± 4 years; mean ± S.E.M.) and ten younger (age 35 ± 4 years) body mass index-matched, obese, normal glucose tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 ± 7.1 vs. 36.5 ± 6.7 kg; P = 0.16), however waist circumference (WC) was not different between groups (104.3 ± 10.3 vs. 102.1 ± 12.6 cm; P = 0.65). Basal fat oxidation was 22% lower (1.42 ± 0.14 vs. 1.17 ± 0.22 mg/kg fat-free mass (FFM)/min; P = 0.03) in older subjects. VO 2 max was also decreased in older individuals (44.6 ± 7.1 vs. 38.3 ± 6.0 ml/kgFFM/min; P = 0.03), but neither insulin sensitivity, lipemia, nor leptinemia were different between groups (P > 0.05). Fat oxidation was most related to age (r = −0.61, P = 0.003) and VO 2 max (r = 0.52, P = 0.01). These data suggest that aging per se is responsible for reduced basal fat oxidation and maximal oxidative capacity in older obese individuals, independent of changes in insulin resistance, body mass, and abdominal fat. This indicates that age, in addition to obesity, is an independent risk factor for weight gain and for the metabolic complications of elevated body fat.