Basal and insulin-regulated free fatty acid and glucose metabolism in humans

These studies were done to examine the effects of body composition, resting energy expenditure (REE), sex, and fitness on basal and insulin-regulated FFA and glucose metabolism. We performed 137 experiments in 101 nondiabetic, premenopausal women and men, ranging from low normal weight to class III obese (BMI 18.0-40.5 kg/m2). Glucose flux was measured using [6-(2)H2]glucose and FFA kinetics with [9,10-(3)H]oleate under either basal (74 experiments) or euglycemic hyperinsulinemic (1.0 mU.kg FFM(-1).min(-1)) clamp conditions (63 experiments). Consistent with our previous findings, REE and sex independently predicted basal FFA flux, whereas fat-free mass was the best predictor of basal glucose flux; in addition, percent body fat was independently and positively associated with basal glucose flux (total r2 = 0.52, P < 0.0001). Insulin-suppressed lipolysis remained significantly associated with REE (r = 0.25, P < 0.05), but percent body fat also contributed (total adjusted r2 = 0.36, P < 0.0001), whereas sex was not significantly related to insulin-suppressed FFA flux. Glucose disposal during hyperinsulinemia was independently associated with peak VO2, percent body fat, and FFA concentrations (total r2 = 0.63, P < 0.0001) but not with sex. We conclude that basal glucose production is independently related to both FFM and body fatness. In addition, hyperinsulinemia obscures the sex differences in FFA release relative to REE, but brings out the effects of fatness on lipolysis.     

Muscle fatty acid oxidative capacity is a determinant of whole body fat oxidation in elderly people

In sedentary elderly people, a reduced muscle fatty acid oxidative capacity (MFOC) may explain a decrease in whole body fat oxidation. Eleven sedentary and seven regularly exercising subjects (65.6 +/- 4. 5 yr) were characterized for their aerobic fitness [maximal O(2) uptake (VO(2 max))/kg fat free mass (FFM)] and their habitual daily physical activity level [free-living daily energy expenditure divided by sleeping metabolic rate (DEE(FLC)/SMR)]. MFOC was determined by incubating homogenates of vastus lateralis muscle with [1-(14)C]palmitate. Whole body fat oxidation was measured by indirect calorimetry over 24 h. MFOC was 40.4 +/- 14.7 and 44.3 +/- 16.3 nmol palmitate. g wet tissue(-1). min(-1) in the sedentary and regularly exercising individuals, respectively (P = nonsignificant). MFOC was positively correlated with DEE(FLC)/SMR (r = 0.58, P < 0. 05) but not with VO(2 max)/kg FFM (r = 0.35, P = nonsignificant). MFOC was the main determinant of fat oxidation during all time periods including physical activity. Indeed, MFOC explained 19.7 and 30.5% of the variance in fat oxidation during walking and during the alert period, respectively (P < 0.05). Furthermore, MFOC explained 23.0% of the variance in fat oxidation over 24 h (P < 0.05). It was concluded that, in elderly people, MFOC may be influenced more by overall daily physical activity than by regular exercising. MFOC is a major determinant of whole body fat oxidation during physical activities and, consequently, over 24 h.     

Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action.

The purpose of this study was to determine the factors contributing to the ability of exercise to enhance insulin-stimulated glucose disposal. Sixteen insulin-resistant nondiabetic and seven Type 2 diabetic subjects underwent two hyperinsulinemic (40 mU x m-2 x min-1) clamps, once without and once with concomitant exercise at 70% peak O2 consumption. Exercise was begun at the start of insulin infusion and was performed for 30 min. Biopsies of the vastus lateralis were performed before and after 30 min of insulin infusion (immediately after cessation of exercise). Exercise synergistically increased insulin-stimulated glucose disposal in nondiabetic [from 4.6 +/- 0.4 to 9.5 +/- 0.8 mg x kg fat-free mass (FFM)-1x min-1] and diabetic subjects (from 4.3 +/- 1.0 to 7.9 +/- 0.7 mg. kg FFM-1x min-1) subjects. The rate of glucose disposal also was significantly greater in each group after cessation of exercise. Exercise enhanced insulin-stimulated increases in glycogen synthase fractional velocity in control (from 0.07 +/- 0.02 to 0.22 +/- 0.05, P < 0.05) and diabetic (from 0.08 +/- 0.03 to 0.15 +/- 0.03, P < 0.01) subjects. Exercise also enhanced insulin-stimulated glucose storage (glycogen synthesis) in nondiabetic (2.9 +/- 0.9 vs. 4.9 +/- 1.1 mg x kg FFM-1x min-1) and diabetic (1.7 +/- 0.5 vs. 4.2 +/- 0.8 mg x kg FFM-1. min-1) subjects. Increased glucose storage accounted for the increase in whole body glucose disposal when exercise was performed during insulin stimulation in both groups; effects of exercise were correlated with enhancement of glucose disposal and glucose storage (r = 0.93, P < 0.001). Exercise synergistically enhanced insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity (P < 0.05) and Akt Ser473 phosphorylation (P < 0.05) in nondiabetic subjects but had little effect in diabetic subjects. The data indicate that exercise, performed in conjunction with insulin infusion, synergistically increases insulin-stimulated glucose disposal compared with insulin alone. In nondiabetic and diabetic subjects, increased glycogen synthase activation is likely to be involved, in part, in this effect. In nondiabetic, but not diabetic, subjects, exercise-induced enhancement of insulin stimulation of the phosphatidylinositol 3-kinase pathway is also likely to be involved in the exercise-induced synergistic enhancement of glucose disposal.     

Cardiorespiratory fitness predicts changes in adiposity in overweight Hispanic boys

We have previously shown that cardiorespiratory fitness predicts increasing fat mass during growth in white and African-American youth, but limited data are available examining this issue in Hispanic youth. Study participants were 160 (53% boys) overweight (BMI>or=85th percentile for age and gender) Hispanic children (mean+/-s.d. age at baseline=11.2+/-1.7 years). Cardiorespiratory fitness, assessed by VO2max, was measured through a maximal effort treadmill test at baseline. Body composition through dual-energy X-ray absorptiometry and Tanner stage through clinical exam were measured at baseline and annually thereafter for up to 4 years. Linear mixed models were used to examine the gender-specific relationship between VO2max and increases in adiposity (change in fat mass independent of change in lean tissue mass) over 4 years. The analysis was adjusted for changes in Tanner stage, age, and lean tissue mass. In boys, higher VO2max at baseline was inversely associated with the rate of increase in adiposity (beta=-0.001, P=0.03); this effect translates to a 15% higher VO2max at baseline resulting in a 1.38 kg lower fat mass gain over 4 years. However, VO2max was not significantly associated with changes in fat mass in girls (beta=0.0002, P=0.31). In overweight Hispanic boys, greater cardiorespiratory fitness at baseline was protective against increasing adiposity. In girls however initial cardiorespiratory fitness was not significantly associated with longitudinal changes in adiposity. These results suggest that cardiorespiratory fitness may be an important determinant of changes in adiposity in overweight Hispanic boys but not in girls.     

Fatty liver in type 2 diabetes mellitus: relation to regional adiposity,fatty acids,and insulin resistance

The current study was undertaken to examine metabolic and body composition correlates of fatty liver in type 2 diabetes mellitus (DM). Eighty-three men and women with type 2 DM [mean body mass index (BMI): 34 +/- 0.5 kg/m2] and without clinical or laboratory evidence of liver dysfunction had body composition assessments of fat mass (FM), visceral adipose tissue (VAT), liver and spleen computed tomography (CT) attenuation (ratio of liver to spleen), muscle CT attenuation, and thigh adiposity; these assessments were also performed in 12 lean and 15 obese nondiabetic volunteers. Insulin sensitivity was measured with a euglycemic insulin infusion (40 mU. m-2. min-1) combined with systemic indirect calorimetry to assess glucose and lipid oxidation, and with infusions of [2H2]glucose for assessment of endogenous glucose production. A majority of those with type 2 DM (63%) met CT criteria for fatty liver, compared with 20% of obese and none of the lean nondiabetic volunteers. Fatty liver was most strongly correlated with VAT (r = -0.57, P < 0.0001) and less strongly but significantly associated with BMI (r = -0.42, P < 0.001) and FM (r = -0.37, P < 0.001), but only weakly associated with subcutaneous adiposity (r = -0.29; P < 0.01). Fatty liver was also correlated with subfascial adiposity of skeletal muscle (r = -0.44; P < 0.01). Volunteers with type 2 DM and fatty liver were substantially more insulin resistant those with type 2 DM but without fatty liver (P < 0.001) and had higher levels of plasma free fatty acids (P < 0.01) and more severe dyslipidemia (P < 0.01), a pattern observed in both genders. Plasma levels of cytokines were increased in relation to fatty liver (r = -0.34; P < 0.01). In summary, fatty liver is relatively common in overweight and obese volunteers with type 2 DM and is an aspect of body composition related to severity of insulin resistance, dyslipidemia, and inflammatory markers.     

Physique, body composition and maximum oxygen consumption of selected soccer players of Kunimi High School, Nagasaki, Japan

This study evaluates the physical and physiological ability of selected soccer players of Kunimi High School in Nagasaki Prefecture, Japan. The Kunimi team is famous for its intensive training, and had won the championship of the All Japan High School Soccer Tournament six times by 2003. We measured physique, body composition, and maximal oxygen uptake of 72 members aged between 16 and 18 years old between 1986 and 1994. They consisted of 66 outfield players (12 forward players, 23 midfielders, 31 defenders) and 6 goalkeepers. Body density was measured by the under-water weighing method, and Brozek's equation was applied to calculate percentage body fat (%Fat, %), fat-free mass (FFM, kg), FFM/height (FFM/Ht, kg.m(-1)), and FFM index (FFM/Ht(3), kg.m(-3)). The following results were obtained: 1. The average of 66 outfield players was 172.7 cm of height, 64.6 kg of weight, 54.0 cm of girth of thigh, and 90.0 cm of girth of hip, 9.3% of %Fat, 58.6 kg of FFM, 33.9 kg.m(-1) of FFM/Ht and 113.8 kg.m(-3) of FFM index. The mean vital capacity was 4.25 L and total lung capacity was 5.58 L. The mean maximal ventilation was 138.7 L.min(-1), VO(2)max was 3.95 L.min(-1), and VO(2)max/Wt was 61.4 ml.kg(-1).min(-1). 2. Goalkeepers were taller and heavier than outfielders, and had a smaller mean value of VO(2)max/Wt than outfielders (p<0.01). 3. For 23 out of the 72 players measured twice with an interval of about one year, FFM increased and %Fat reduced significantly, while V(E)max, VO(2)max and VO(2)max/Wt did not change. Kunimi players of the present study had as large a VO(2)max/Wt as local players, and a similar or slightly smaller VO(2)max/Wt than national-level players. They had similar %Fat and a similar VO(2)max/Wt with professional soccer players in England (Davis et al., 1992) while they had much smaller physiques.     

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.     

Fat-free mass and excess post-exercise oxygen consumption in the 40 minutes after short-duration exhaustive exercise in young male Japanese athletes

The relationship between fat-free mass (FFM) and excess post-exercise oxygen consumption (EPOC) has not been well researched because of the relatively small number of subjects studied. This study investigated the effects of FFM on EPOC and EPOC/maximum oxygen consumption. 250 Japanese male athletes between 16 and 21 years old from Nagasaki prefecture had their EPOC measured up to 40 minutes after short-duration exhaustive exercise. The value was named as EPOC40 min. The proportions of EPOC up to 1, 3, 6, 10, and 25 minutes to EPOC40 min were calculated and named as P1, P3, P6, P10, and P25, respectively. Body size and composition, VO2max and resting metabolic rate (RMR) were also measured. Mean EPOC40 min was 9.04 L or 158 ml/kg FFM. EPOC40 min was related to FFM (r=0.55, p<0.001) and VO2max (r=0.37, p<0.001). The ratio of EPOC40 min to VO2max was related to FFM (r=0.28, p<0.001). P1, P3, P6, P10, and P25 were negatively related to EPOC40 min/FFM, EPOC40 min/VO2max, and FFM. Athletes who had larger FFM had larger EPOC40 40 min and EPOC40 40 min/VO2max, and smaller P1, P3, P10, and P25.     

Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU x m(-2) x min(-1)) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-D-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 +/- 0.4 vs. 2.3 +/- 0.5 micromol x kg tissue(-1) x min(-1), P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal (r2 = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area (r = -0.75, P = 0.008), and whole body glucose disposal (r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.     

The relationship between maximal oxygen uptake and glucose tolerance/insulin response ratio in normal young men.

Maximal oxygen uptake (VO2max.), glucose tolerance (K-value), and insulin response (IRI-area) were studied in seventeen young, non-obese, non-diabetic males. The ratio between K-value and IRI-area correlated significantly with VO2 max. (r = 0.70, p less than 0.01) also when differences in body fat mass were eliminated by partial correlation analysis (r = 0.56, p less than 0.05). Subjects with a high VO2 max. thus maintained a given glucose tolerance with a lower insulin response than did subjects in whom VO2 max. was low.     

Effects of Adiposity and 30 Days of Caloric Restriction Upon Protein Metabolism in Moderately vs. Severely Obese Women

Protein metabolism adapts during caloric restriction (CR) to minimize protein loss, and it is unclear whether greater fat stores favorably affect this response. We sought to determine whether protein metabolism is related to degree of obesity and whether the response to CR is impacted by pre‐CR adiposity level. Whole body protein metabolism was studied in 12 obese women over a wide range of BMI (30–53 kg/m²) as inpatients using [1‐¹³C]leucine as a tracer following 5 days of a weight‐maintaining diet and then after 30 days of CR (1,400 kcal deficit with maintained protein intake). When expressed as total rates, per body weight (BW) or per fat‐free mass (FFM), leucine rate of appearance (Ra), and nonoxidative leucine disposal (NOLD) were significantly higher in the individuals with a greater degree of obesity (P < 0.05). Leucine oxidation (Rox) was also higher in more highly obese women when expressed as a total rate (P < 0.05) but not if expressed per BW or FFM. CR reduced BW, FFM, and fat mass (P < 0.001), and declines were relatively similar between individuals. CR reduced Ra (P < 0.001), NOLD (P < 0.01), and Rox (P < 0.05), and the relative decline was not affected by differences in fat mass. CR‐induced declines were significant even when Ra and NOLD were normalized to BW or FFM. We conclude that fat mass, like FFM, is a key determinant of protein turnover. However, during CR, higher fat mass does not favorably alter the response of protein metabolism and does not mitigate the loss of FFM.     

Scaling of maximal oxygen uptake by lower leg muscle volume in boys and men.

The aim of this study was to critically examine the influence of body size on maximal oxygen uptake (VO2 max) in boys and men using body mass (BM), estimated fat-free mass (FFM), and estimated lower leg muscle volume (Vol) as the separate scaling variables. VO2 max and an in vivo measurement of Vol were assessed in 15 boys and 14 men. The FFM was estimated after percentage body fat had been predicted from population-specific skinfold measurements. By using nonlinear allometric modeling, common body size exponents for BM, FFM, and Vol were calculated. The point estimates for the size exponent (95% confidence interval) from the separate allometric models were: BM 0.79 (0.53-1.06), FFM 1.00 (0.78-1.22), and Vol 0.64 (0.40-0.88). For the boys, substantial residual size correlations were observed for VO2 max/BM0.79 and VO2 max/FFM1.00, indicating that these variables did not correctly partition out the influence of body size. In contrast, scaling by Vol0.64 led to no residual size correlation in boys or men. Scaling by BM is confounded by heterogeneity of body composition and potentially substantial differences in the mass exponent between boys and men. The FFM is precluded as an index of involved musculature because Vol did not represent a constant proportion of FFM [Vol proportional, variantFFM1.45 (95% confidence interval, 1.13-1.77)] in the boys (unlike the men). We conclude that Vol, as an indicator of the involved muscle mass, is the most valid allometric denominator for the scaling of VO2 max in a sample of boys and men heterogeneous for body size and composition.     

Diversity of Insulin Resistance in Monkeys with Normal Glucose Tolerance

Insulin resistance has been proposed as a critical factor in the development of Type II diabetes, hypertension, dyslipidemia, and coronary artery disease. However, even in normal healthy individuals, a wide range of in vivo insulin action has been found. In the present study we sought to examine this heterogeneity in Insulin action in both normal and spontaneously obese nonhuman primates. Maximal insulin responsiveness as measured by a hyperinsulinemic euglycemic clamp, fasting plasma glucose, and insulin levels, β-cell insulin response to glucose, glucose tolerance, and adiposity were measured in 22 male rhesus monkeys. Results showed that lean animals (body fat ≤ 22%) had higher insulin-stimulated glucose uptake (M rate: 14.42±1.8 mg/kg FFM/min) compared to obese (8.08±0.8). The obese monkeys, with 23–49% body fat, had a wide range of M values (5.32-14.29 mg/kg FFM/min) which showed no relationship to degree of adiposity. In all monkeys, M values had a strong inverse correlation with fasting plasma insulin levels (r=-0.76; p<0.001), but not with fasting glucose or glucose disappearance rate. We conclude that neither degree of obesity above a critical threshold nor range of glucose tolerance is related to insulin resistance; however, in individuals with normal glucose tolerance an early reliable indicator of defective insulin action appears to be fasting insulin concentration. Longitudinal determination of basal insulin levels obtained under standardized conditions so as to minimize extraneous variability is likely to strengthen the ability to predict insulin resistance and possible later development of overt Type II diabetes.     

Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis

Although chronic hyperinsulinemia has been shown to induce insulin resistance, the basic cellular mechanisms responsible for this phenomenon are unknown. The present study was performed 1) to determine the time-related effect of physiological hyperinsulinemia on glycogen synthase (GS) activity, hexokinase II (HKII) activity and mRNA content, and GLUT-4 protein in muscle from healthy subjects, and 2) to relate hyperinsulinemia-induced alterations in these parameters to changes in glucose metabolism in vivo. Twenty healthy subjects had a 240-min euglycemic insulin clamp study with muscle biopsies and then received a low-dose insulin infusion for 24 (n = 6) or 72 h (n = 14) (plasma insulin concentration = 121 +/- 9 or 143 +/- 25 pmol/l, respectively). During the baseline insulin clamp, GS fractional velocity (0.075 +/- 0.008 to 0.229 +/- 0.02, P < 0.01), HKII mRNA content (0.179 +/- 0.034 to 0.354 +/- 0.087, P < 0.05), and HKII activity (2.41 +/- 0.63 to 3.35 +/- 0.54 pmol x min(-1) x ng(-1), P < 0.05), as well as whole body glucose disposal and nonoxidative glucose disposal, increased. During the insulin clamp performed after 24 and 72 h of sustained physiological hyperinsulinemia, the ability of insulin to increase muscle GS fractional velocity, total body glucose disposal, and nonoxidative glucose disposal was impaired (all P < 0.01), whereas the effect of insulin on muscle HKII mRNA, HKII activity, GLUT-4 protein content, and whole body rates of glucose oxidation and glycolysis remained unchanged. Muscle glycogen concentration did not change [116 +/- 28 vs. 126 +/- 29 micromol/kg muscle, P = nonsignificant (NS)] and was not correlated with the change in nonoxidative glucose disposal (r = 0.074, P = NS). In summary, modest chronic hyperinsulinemia may contribute directly (independent of change in muscle glycogen concentration) to the development of insulin resistance by its impact on the GS pathway.     

Relationship between fat-to-fat-free mass ratio and decrements in leg strength after downhill running.

The purpose of this study was to determine whether greater body fat mass (FM) relative to lean mass would result in more severe muscle damage and greater decrements in leg strength after downhill running. The relationship between the FM-to-fat-free mass ratio (FM/FFM) and the strength decline resulting from downhill running (-11% grade) was investigated in 24 male runners [age 23.4 +/- 0.7 (SE) yr]. The runners were divided into two groups on the basis of FM/FFM: low fat (FM/FFM = 0.100 +/- 0.008, body mass = 68.4 +/- 1.3 kg) and normal fat (FM/FFM = 0.233 +/- 0.020, body mass = 76.5 +/- 3.3 kg, P < 0.05). Leg strength was reduced less in the low-fat (-0.7 +/- 1.3%) than in the normal-fat individuals (-10.3 +/- 1.5%) 48 h after, compared with before, downhill running (P < 0.01). Multiple linear regression analysis revealed that the decline in strength could be predicted best by FM/FFM (r2 = 0.44, P < 0.05) and FM-to-thigh lean tissue cross-sectional area ratio (r2 = 0.53, P < 0.05), with no additional variables enhancing the prediction equation. There were no differences in muscle glycogen, creatine phosphate, ATP, or total creatine 48 h after, compared with before, downhill running; however, the change in muscle glycogen after downhill running was associated with a higher FM/FFM (r = -0.56, P < 0.05). These data suggest that FM/FFM is a major determinant of losses in muscle strength after downhill running.     

Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study.

The aim of the present study was to establish fat oxidation rates over a range of exercise intensities in a large group of healthy men and women. It was hypothesised that exercise intensity is of primary importance to the regulation of fat oxidation and that gender, body composition, physical activity level, and training status are secondary and can explain part of the observed interindividual variation. For this purpose, 300 healthy men and women (157 men and 143 women) performed an incremental exercise test to exhaustion on a treadmill [adapted from a previous protocol (Achten J, Venables MC, and Jeukendrup AE. Metabolism 52: 747-752, 2003)]. Substrate oxidation was determined using indirect calorimetry. For each individual, maximal fat oxidation (MFO) and the intensity at which MFO occurred (Fat(max)) were determined. On average, MFO was 7.8 +/- 0.13 mg.kg fat-free mass (FFM)(-1).min(-1) and occurred at 48.3 +/- 0.9% maximal oxygen uptake (Vo(2 max)), equivalent to 61.5 +/- 0.6% maximal heart rate. MFO (7.4 +/- 0.2 vs. 8.3 +/- 0.2 mg.kg.FFM(-1).min(-1); P < 0.01) and Fat(max) (45 +/- 1 vs. 52 +/- 1% Vo(2 max); P < 0.01) were significantly lower in men compared with women. When corrected for FFM, MFO was predicted by physical activity (self-reported physical activity level), Vo(2 max), and gender (R(2) = 0.12) but not with fat mass. Men compared with women had lower rates of fat oxidation and an earlier shift to using carbohydrate as the dominant fuel. Physical activity, Vo(2 max), and gender explained only 12% of the interindividual variation in MFO during exercise, whereas body fatness was not a predictor. The interindividual variation in fat oxidation remains largely unexplained.     

Association between muscular strength and metabolic risk in Japanese women, but not in men

We examined whether cardiorespiratory fitness (maximal oxygen uptake, VO(2)max) and muscular strength (grip strength) are associated with individual and clustered metabolic risk factors independently of abdominal adiposity in Japanese men (n=110) and women (n=110) aged 20-69 years. Blood pressure, triglycerides (TG), HDL cholesterol, and fasting plasma glucose (FPG) were assessed and metabolic risk score was calculated, which is the sum of the z scores for each individual risk factor. Waist circumference was measured and the area of visceral fat was assessed by MRI. Multiple linear regression analysis revealed that VO(2)max was inversely associated with TG in men (p<0.05) and grip strength was negatively associated with FPG and metabolic risk score in women (p<0.001 and p<0.05, respectively), independently of waist circumference. Adjusting for visceral fat instead of waist circumference, similar results were obtained in women (p<0.01 and p<0.05, respectively), but the association between VO(2)max and TG in men was attenuated to nonsignificant. This cross-sectional study demonstrates that muscular strength is inversely associated with plasma glucose levels and clustered metabolic risk factors independently of abdominal adiposity in Japanese women, but not in men.     

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 +/- 2 yr, BMI = 25.5 +/- 0.9 kg/m(2)) and low (IR; n = 18, 12 females and 6 males, age 45 +/- 2 yr, P = 0.49, BMI = 27.5 +/- 1.1 kg/m(2), P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU.min(-1).m(-2)) isoglycemic clamp tests. M(100-120 min) was higher in IS (10.7 +/- 0.7) than in IR (4.4 +/- 0.2 mg.min(-1).kg(-1), P < 10(-9)), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 +/- 6% vs. IS: 82 +/- 5%, P < 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24-28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 +/- 26 pg/ml vs. IS: 469 +/- 23 pg/ml, P < 0.02). Clamp insulin infusion reduced plasma obestatin to approximately 81% of basal values in IS (P < 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M (r = 0.34, P = 0.04), HDL cholesterol (r = 0.45, P = 0.01), and plasma ghrelin concentrations (r = 0.80, P < 0.000001) and negatively with measures of adiposity, plasma FFA during clamp (r = -0.42, P < 0.01), and systolic blood pressure (r = -0.33, P < 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.     

Effect of prolonged training period on plasma adiponectin in elite male rowers.

Adiponectin is secreted by adipocytes and has been implicated in the regulation of energy homeostasis. Vigorous training program represents a physical stress condition in which heavy changes in energy expenditure might increase adiponectin concentration in athletes. Therefore, the aim of the present study was to investigate if there are changes in fasting adiponectin concentration during preparatory period in elite male rowers. Twelve rowers (mean and SD; age: 20.8+/-3.0 years; height: 192.9+/-4.7 cm; body mass: 91.9+/-5.3 kg; body fat percentage: 11.9+/-1.4%) were tested seven times over a 24-week training season. In addition to adiponectin, leptin, insulin, growth hormone, and glucose values were evaluated. Maximal oxygen consumption (VO (2 max)) and aerobic power (Pa (max)) were determined before and after the training period. Training was mainly organized as low-intensity prolonged training. Significant increases in VO (2 max) (by 3.2+/-1.8%; from 6.2+/-0.5 to 6.4+/-0.4 l/min), VO (2 max/kg) (by 2.2+/-2.0%; from 67.9+/-3.0 to 69.4+/-3.0 ml/min/kg) and Pa (max) (by 4.6+/-6.3%; from 444.6+/-39.1 to 465.8+/-25.0 W) were observed after the 24-week period. All measured body compositional values were similar to pretraining values after the training period. Fasting adiponectin did not change during the preparatory period. Likewise, leptin, insulin, growth hormone, and glucose values were not significantly changed after the training period. Adiponectin concentration was significantly correlated (all p<0.05) with body mass (r=-0.40), body fat mass (r=-0.33), body fat free mass (r=0.38), and leptin (r=-0.31) values. In conclusion, fasting adiponectin does not change throughout the prolonged training period in elite male rowers despite substantial changes in training volume. Further studies are needed to clarify possible mechanisms by which adiponectin might influence energy homeostasis during heavy training in elite athletes.     

Maximal aerobic capacity across age in healthy Hispanic and Caucasian women.

We tested the hypothesis that the age-related decline in maximal aerobic capacity, as measured by maximal oxygen uptake (VO(2 max)), is greater in Hispanic than in Caucasian women. We studied 146 healthy sedentary women aged 20-75 yr: 53 Hispanic (primarily of Mexican descent) and 93 Caucasian (non-Hispanic white). The groups did not differ in mean age, body mass, percent body fat, estimated physical activity-related energy expenditure, or education-based socioeconomic status (SES). During maximal exercise, respiratory exchange ratio, rating of perceived exertion, and percent predicted maximal heart rate were similar across age and ethnicity, suggesting equivalent maximum voluntary efforts in all subjects. VO(2 max) (ml x kg(-1) x min(-1)) was inversely related to age (P < 0.01) in Caucasian (r =-0.68) and Hispanic (r = -0.61) women. The absolute rate of decline in VO(2 max) with age was the same in the two groups (-0.31 ml x kg(-1) x min(-1) x yr(-1)). The relative rate of decline (% from age 25 yr) also was similar in the Caucasian (-9.0%) and Hispanic (-9.2%) women. When subjects of all ages were pooled, mean levels of VO(2 max) were similar in the two groups (approximately 28 ml x kg(-1) x min(-1)). These results, the first to our knowledge in Hispanics, indicate that mean levels of VO(2 max), as well as the rate of decline in VO(2 max) with age, are similar in healthy sedentary Hispanic and Caucasian women of similar SES. Thus it does not appear that Hispanic ethnicity per se modulates maximal aerobic capacity in this population.