Effects of Obesity on Substrate Utilization during Exercise

Objective: The capacity for lipid and carbohydrate (CHO) oxidation during exercise is important for energy partitioning and storage. This study examined the effects of obesity on lipid and CHO oxidation during exercise. Research Methods and Procedures: Seven obese and seven lean [body mass index (BMI), 33 ± 0.8 and 23.7 ± 1.2 kg/m², respectively] sedentary, middle‐aged men matched for aerobic capacity performed 60 minutes of cycle exercise at similar relative (50% Vo _2max) and absolute exercise intensities. Results: Obese men derived a greater proportion of their energy from fatty‐acid oxidation than lean men (43 ± 5% 31 ± 2%; p = 0.02). Plasma fatty‐acid oxidation determined from recovery of infused [0.15 μmol/kg fat‐free mass (FFM) per minute] [1‐¹³C]‐palmitate in breath CO₂ was similar for obese and lean men (8.4 ± 1.1 and 29 ± 15 μmol/kg FFM per minute). Nonplasma fatty‐acid oxidation, presumably, from intramuscular sources, was 50% higher in obese men than in lean men (10.0 ± 0.6 versus 6.6 ± 0.8 μmol/kg FFM per minute; p < 0.05). Systemic glucose disposal was similar in lean and obese groups (33 ± 8 and 29 ± 15 μmol/kg FFM per minute). However, the estimated rate of glycogen‐oxidation was 50% lower in obese than in lean men (61 ± 12 versus 90 ± 6 μmol/kg FFM per minute; p < 0.05). Discussion: During moderate exercise, obese sedentary men have increased rates of fatty‐acid oxidation from nonplasma sources and reduced rates of CHO oxidation, particularly muscle glycogen, compared with lean sedentary men.     

Lifestyle Intervention and Fatty Acid Metabolism in Glucose‐Intolerant Subjects

Objective: Free fatty acid (FFA) oxidation is reduced in subjects with type 2 diabetes mellitus and impaired glucose tolerance (IGT). Weight reduction does not improve these impairments. Because exercise training is known to increase fatty acid (FA) oxidation, we investigated whether a combined diet and physical activity intervention program can improve FA oxidation in subjects with IGT. Research Methods and Procedures: Sixteen subjects with IGT were studied before and after 1 year of a lifestyle intervention program [nine intervention (INT) subjects, seven controls (CON)]. INT subjects received regular (i.e., every 3 months) dietary advice and were stimulated to increase their level of physical activity. Glucose tolerance, anthropometric characteristics, and substrate use at rest and during exercise were evaluated before and after 1 year. Substrate oxidation was measured at rest and during moderate intensity exercise using indirect calorimetry in combination with stable isotope infusion ([U‐¹³C]palmitate and [6, 6‐²H₂‐]glucose). Results: After 1 year, no differences were seen in substrate use at rest. During exercise, total fat and plasma FFA oxidation were slightly increased in the INT group and decreased in the CON group, with the change being significantly different (change after 1 year: INT, +2.0 ± 1.4 and +1.9 ± 0.9 μmol/kg per minute; CON, ?3.5 ± 1.6 and ?1.8 ± 0.5 μmol/kg per minute for total and plasma FFA, respectively; p < 0.05). Discussion: A combined diet and physical activity intervention program can prevent further deterioration of impaired FA oxidation during exercise in subjects with IGT.     

Inflexibility in Intramuscular Triglyceride Fractional Synthesis Distinguishes Prediabetes From Obesity in Humans

Whether intramuscular triglyceride (IMTG) concentration or flux is more important in the progression to type 2 diabetes is controversial. Therefore, this study examined IMTG concentration, as well as its fractional synthesis rate (FSR), in obese people with normal glucose tolerance (NGT; n = 20) vs. obese people with prediabetes (PD; n = 19), at rest and during exercise. Insulin action and secretion were assessed using an intravenous glucose tolerance test. [U‐¹³C]palmitate was infused for 4 h before and throughout 1.5 h of treadmill walking at 50% VO_2max. IMTG concentration was measured by gas chromatograph/mass spectrometer, and FSR by gas chromatography–combustion isotope ratio mass spectrometer, from muscle biopsies taken immediately before and after exercise. Basal IMTG concentration was higher (43 ± 5.7 vs. 27 ± 3.9 mg/mg dry weight, P = 0.03) and FSR trended lower (0.23 ± 0.04 vs. 0.32 ± 0.05/h, P = 0.075), as did insulin action (S_i; 2.9 ± 0.43 vs. 3.3 ± 0.35 × 10^?4/mU/ml, P = 0.07), in PD vs. NGT. IMTG concentration did not change significantly during exercise, but was no longer different in PD vs. NGT (45 ± 7.7 vs. 37 ± 5.8 mg/mg dry weight, P = 0.41). IMTG FSR suppressed during exercise in NGT (?81% to 0.06 ± 0.13/h, P = 0.02), but not PD (+4% to 0.24 ± 0.13%/h, P = 0.95). Palmitate oxidation was similar during rest (P = 0.92) and exercise (P = 0.94) between groups, but its source appeared different with more coming from muscle at rest and plasma during exercise in NGT, whereas the converse was true in PD. Altogether, higher basal IMTG concentration that is metabolically inflexible distinguishes obese people with PD from those with NGT.     

Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

The Effect of Low‐Intensity Exercise Training on Fat Metabolism of Obese Women

Objective: Previous studies have shown that fat metabolism is different in upper body (UB) and lower body (LB) obese women. The present study investigated whether the effect of low‐intensity exercise training on fat metabolism is different in UB and LB obese premenopausal women. Research Methods and Procedures: Twenty‐one healthy, premenopausal women with either LB obesity (waist‐to‐hip ratio of ≤0.79; n = 8) or UB obesity (waist‐to‐hip ratio of ≥0.85; n = 13) participated in the present study. The UB obese women were matched and randomly divided in an exercise training group (UB) and a nonexercising control group (UB‐C). Subjects in the UB and LB groups participated in a low‐intensity exercise training program (40% Vo ₂max) three times per week for 12 weeks. Before and after the intervention, measurements of fat metabolism at rest and during exercise, body composition, and maximal aerobic capacity were performed. Results: Exercise training did not change the respiratory exchange ratio at rest in the UB and LB groups. During exercise, relative fat oxidation increased in the UB group by 19% (p < 0.05), whereas no change in the LB and UB‐C groups was found. Plasma free fatty acid oxidation did not change by exercise training, and nonplasma fatty acid oxidation tended to increase in the UB group compared with the UB‐C group (p = 0.08). Discussion: Low‐intensity exercise training increased the contribution of fat oxidation to total energy expenditure during exercise but not at rest in UB obese women. Exercise training had no significant effect on fat metabolism in the LB obese women.     

Altered Intramuscular Lipid Metabolism Relates to Diminished Insulin Action in Men,but Not Women,in Progression to Diabetes

Whether sex differences in intramuscular triglyceride (IMTG) metabolism underlie sex differences in the progression to diabetes are unknown. Therefore, the current study examined IMTG concentration and fractional synthesis rate (FSR) in obese men and women with normal glucose tolerance (NGT) vs. those with prediabetes (PD). PD (n = 13 men and 7 women) and NGT (n = 7 men and 12 women) groups were matched for age and anthropometry. Insulin action was quantified using a hyperinsulinemic‐euglycemic clamp with infusion of [6,6^?2H₂]‐glucose. IMTG concentration was measured by gas chromatography/mass spectrometry (GC/MS) and FSR by GC/combustion isotope ratio MS (C‐IRMS), from muscle biopsies taken after infusion of [U^?13C]palmitate during 4 h of rest. In PD men, the metabolic clearance rate (MCR) of glucose was lower during the clamp (4.71 ± 0.77 vs. 8.62 ± 1.26 ml/kg fat‐free mass (FFM)/min, P = 0.04; with a trend for lower glucose rate of disappearance (Rd), P = 0.07), in addition to higher IMTG concentration (41.2 ± 5.0 vs. 21.2 ± 3.4 µg/mg dry weight, P ≤ 0.01), lower FSR (0.21 ± 0.03 vs. 0.42 ± 0.06 %/h, P ≤ 0.01), and lower oxidative capacity (P = 0.03) compared to NGT men. In contrast, no difference in Rd, IMTG concentration, or FSR was seen in PD vs. NGT women. Surprisingly, glucose Rd during the clamp was not different between NGT men and women (P = 0.25) despite IMTG concentration being higher (42.6 ± 6.1 vs. 21.2 ± 3.4 µg/mg dry weight, P = 0.03) and FSR being lower (0.23 ± 0.04 vs. 0.42 ± 0.06 %/h, P = 0.02) in women. Alterations in IMTG metabolism relate to diminished insulin action in men, but not women, in the progression toward diabetes.     

Skeletal muscle fat oxidation is increased in African-American and white women after 10 days of endurance exercise training

Objective: Obesity is associated with lower rates of skeletal muscle fatty acid oxidation (FAO), which is linked to insulin resistance. FAO is reduced further in obese African‐American (AAW) vs. white women (CW) and may also be lower in lean AAW vs. CW. In lean CW, endurance exercise training (EET) elevates the oxidative capacity of skeletal muscle. Therefore, we determined whether EET would elevate skeletal muscle FAO similarly in AAW and CW with a lower lipid oxidative capacity. Research Methods and Procedures: In vitro rates of FAO were assessed in rectus abdominus muscle strips using [1‐¹⁴C] palmitate (Pal) from lean AAW [BMI = 24.2 ± 0.9 (standard error) kg/m²] and CW (23.6 ± 0.8 kg/m²) undergoing voluntary abdominal surgery. Lean AAW (22 ± 0.9 kg/m²) and CW (24 ± 0.8 kg/m²) and obese AAW (36 ± 1.2 kg/m²) and CW (40 ± 1.3 kg/m²) underwent 10 consecutive days of EET on a cycle ergometer (60 min/d, 75% peak oxygen uptake). FAO was measured in vastus lateralis homogenates as captured ¹⁴CO₂ using [1‐¹⁴C] Pal, palmitoyl‐CoA (Pal‐CoA), and palmityl‐carnitine (Pal‐Car). Results: Muscle strip experiments showed suppressed rates of FAO (p = 0.03) in lean AAW vs. CW. EET increased the rates of skeletal muscle Pal oxidation (p = 0.05) in both lean AAW and CW. In obese subjects, Pre‐EET Pal (but not Pal‐CoA or Pal‐Car) oxidation was lower (p = 0.05) in AAW vs. CW. EET increased Pal oxidation 100% in obese AAW (p < 0.05) and 59% (p < 0.05) in obese CW. Similar increases (p < 0.05) in post‐EET FAO were observed for Pal‐CoA and Pal‐Car in both groups. Discussion: Both lean and obese AAW possess a lower capacity for skeletal muscle FAO, but EET increases FAO similarly in both AAW and CW. These data suggest the use of EET for treatment against obesity and diabetes for both AAW and CW.     

Aerobic exercise is necessary to improve glucose utilization with moderate weight loss in women

Objective: To determine the effects of weight loss (WL) alone and combined with aerobic exercise on visceral adipose tissue (VAT), intramuscular fat, insulin‐stimulated glucose uptake, and the rate of decline in free fatty acid (FFA) concentrations during hyperinsulinemia. Research Methods and Procedures: We studied 33 sedentary, obese (BMI = 32 ± 1 kg/m²) postmenopausal women who completed a 6‐month (three times per week) program of either WL alone (n = 16) or WL + aerobic exercise (AEX) (n = 17). Glucose utilization (M) was measured during a 3‐hour hyperinsulinemic‐euglycemic clamp (40 mU/m² per minute). M/I, the amount of glucose metabolized per unit of plasma insulin (I), was used as an index of insulin sensitivity. Results: Body weight, total fat mass, and percentage fat decreased similarly in both groups (p < 0.01). VAT, subcutaneous abdominal adipose tissue, mid‐thigh subcutaneous fat, and intramuscular fat decreased to a similar extent in both groups and between 14% and 27% after WL and WL+AEX (p < 0.05). WL alone did not change M or M/I; however, M and M/I increased 15% and 21% after WL+AEX (p < 0.05). Fasting concentrations and rate of decline of FFA did not change in either group. In stepwise regression models to determine the independent predictors of changes in M and M/I, the change in VAT was the single independent predictor of M (r² = 0.30) and M/I (r² = 0.33). Discussion: Intramuscular fat decreases similarly with 6 months of moderate WL alone or with aerobic exercise in postmenopausal women. In contrast, only WL combined with exercise results in increased glucose utilization and insulin sensitivity. These findings should be validated in a larger population.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.     

The Effect of CYP19 and COMT Polymorphisms on Exercise‐Induced Fat Loss in Postmenopausal Women

Objective:To examine whether genetic polymorphisms in CYP19 [intron 4 (TTTA)_n; n = 7 to 13 and a 3‐base pair deletion, which is in strong linkage disequilibrium with the seven repeat] and COMT (Val^108/158Met) modified the change in BMI, total and percentage body fat, or subcutaneous and intra‐abdominal fat during a year‐long exercise intervention trial. These genes metabolize estrogens and androgens, which are important in body fat regulation. Research Methods and Procedures: A randomized intervention trial was used, with an intervention goal of 225 min/wk of moderate‐intensity exercise for one year. Participants (n = 173) were postmenopausal, 50 to 75 years old, sedentary, overweight or obese, and not taking hormone therapy at baseline. Results: Exercisers with two vs. no CYP19 11‐repeat alleles had a larger decrease in total fat (?3.1 kg vs. ?0.5 kg, respectively, p = 0.01) and percentage body fat (?2.4% vs. ?0.6%, respectively, p = 0.001). Exercisers with the COMT Met/Met vs. Val/Val genotype had a smaller decrease in percentage fat (?0.7% vs. ?1.9%, respectively, p = 0.05). Among exercisers, women with the COMT Val/Val genotype and at least one copy of the CYP19 11‐repeat allele vs. those with neither genotype/allele had a significantly larger decrease in BMI (?1.0 vs. +0.1 kg/m², respectively, p = 0.009), total fat (?2.9 vs. ?0.5 kg, respectively, p = 0.004), and percentage body fat (?2.6% vs. ?0.4%, respectively, p < 0.001). Discussion: Genetic polymorphisms in CYP19 and COMT may be important for body fat regulation and possibly modify the effect of exercise on fat loss in postmenopausal women.     

Racial Differences in Metabolic Predictors of Obesity among Postmenopausal Women

NICKLAS, BARBARA S., DORA M. BERMAN, DAWN C. DAVIS, C. LYNNE DOBROVOLNY, AND KAREN E. DENNIS. Racial differences in metabolic predictors of obesity among postmenopausal women. Ober Res. Objective: This study determined whether there are racial differences in resting metabolic rate (RMR), fat oxidation, and maximal oxygen consumption (VO,max) in obese [body mass index (BMI = 34±2 kg/m²)], postmenopausal (58±2 years) women. Research Methods and Procedures: Twenty black and 20 white women were matched for fat mass and lean mass (LM), as determined by dual energy X-ray absorptiometry. RMR and fat oxidation were measured by indirect calorimetry in the early morning after a 12-hour fast using the ventilated hood technique. VO₂max was measured on a treadmill during a progressive exercise test to voluntary exhaustion. Results: RMR, adjusted for differences in LM, was 5% higher in white than black women (1566±27 and 1490±26 kcal/day, respectively; p<0. 05); and fat oxidation rate was 17% higher in white than black women (87±4 and 72±3 g/day, respectively; p<0. 01). VO₂max (L/minute) was 150 mL per minute (8%) higher (p<0. 05) in white than black women. VO₂max correlated with LM in black (r = 0. 44, p = 0. 05) and white (r=0. 53, p<0. 05) women, but the intercept of the regression line was higher in white than black women (p<0. 05), with no significant difference in slopes. In a multiple regression model including race, body weight, LM, and age, LM was the only independent predictor of RMR (r² = 0. 46, p<0. 0001), whereas race was the only independent predictor of fat oxidation (r² = 0. 18,p<0. 05). The best predictors of VO,max were LM (r² = 0. 22, p<0. 05) and race (cumulative r² = 0. 30, p<0. 05). Discussion: These results show there are racial differences in metabolic predictors of obesity. Determination of whether these ethnic differences lead to, or are an effect of, obesity status or other lifestyle factors requires further study.     

A low‐glycemic diet lifestyle intervention improves fat utilization during exercise in older obese humans

Objective: To determine the influence of dietary glycemic index on exercise training‐induced adaptations in substrate oxidation in obesity. Design and Methods: Twenty older, obese individuals undertook 3 months of fully supervised aerobic exercise and were randomized to low‐ (LoGIX) or high‐glycemic (HiGIX) diets. Changes in indirect calorimetry (VO₂; VCO₂) were assessed at rest, during a hyperinsulinemic‐euglycemic clamp, and during submaximal exercise (walking: 65% VO₂max, 200 kcal energy expenditure). Intramyocellular lipid (IMCL) was measured by ¹H‐magnetic resonance spectroscopy. Results: Weight loss (?8.6 ± 1.1%) and improvements (P < 0.05) in VO₂max, glycemic control, fasting lipemia, and metabolic flexibility were similar for both LoGIX and HiGIX groups. During submaximal exercise, energy expenditure was higher following the intervention (P < 0.01) in both groups. Respiratory exchange ratio during exercise was unchanged in the LoGIX group but increased in the HiGIX group (P < 0.05). However, fat oxidation during exercise expressed in relation to changes in body weight was increased in the LoGIX group (+10.6 ± 3.6%; P < 0.05). Fasting IMCL was unchanged, however, extramyocellular lipid was reduced (P < 0.05) after LoGIX. Conclusions: A LoGIX/exercise weight‐loss intervention increased fat utilization during exercise independent of changes in energy expenditure. This highlights the potential therapeutic value of low‐glycemic foods for reversing metabolic defects in obesity.     

Effects of Dinner Composition on Postprandial Macronutrient Oxidation in Prepubertal Girls

Objective: To see whether a fat‐rich (50%) evening meal promoted fat oxidation and a different spontaneous food intake on the following day at breakfast than a meal with a lower fat content (20%) in 10 prepubertal obese girls. Research Methods and Procedures: The postabsorptive and postprandial (10.5 hours) energy expenditure after a low‐fat (LF) (20% fat, 68% carbohydrate, 12% protein) and an isocaloric (2.1 MJ) and isoproteic high‐fat (HF; 50% fat, 38% carbohydrate, 12% protein) meal were measured by in direct calorimetry. Results: Fat oxidation was not significantly different after the two meals [LF, 31 ± 9 vs. HF, 35 ± 9 g/10.5 hours, p = not significant (NS)]. The girls oxidized 1.8 ± 0.9 times more fat than that ingested (11.1 grams) with the LF meal vs. 0.3 ± 0.3 times more fat than that ingested (27.1 grams) with the HF meal (p < 0.001). Carbohydrate oxidation was significantly higher after an LF than an HF meal (39 ± 12 vs. 29 ± 9 g/10.5 hours, p < 0, 05). At breakfast, the girls spontaneously ingested a similar amount of energy (1.5 ± 0.7 vs. 1.5 ± 0.6 MJ, p = NS) and macronutrient proportions (fat, 23% vs. 26%, p = NS; protein, 9% vs. 10%; carbohydrate, 68% vs. 64%,) independently of their having eaten an HF or an LF dinner. Discussion: An HF dinner did not stimulate fat oxidation, and no compensatory effect in spontaneous food intake was observed during breakfast the following morning. Cumulated total fat oxidation after dinner was higher than total fat ingested at dinner, but a much larger negative fat balance was observed after the LF meal. Spontaneous energy and nutrient intakes at breakfast were similar after LF and HF isocaloric, isoproteic dinners. This study points out the lack of sensitivity of short‐term fat balance to subsequently readjust fat intake and emphasizes the importance of an LF meal to avoid transient positive fat imbalance.     

Association between television in bedroom and adiposity throughout adolescence

Objective: The objective was to determine if having a television (TV) in the bedroom is associated with physical activity (PA), TV/video viewing, and adiposity throughout adolescence. Research Methods and Procedures: Longitudinal data (September 2002 through June 2005) were analyzed of 379 initially 12‐year‐old French adolescents participating as controls in the Intervention Centered on Adolescents’ Physical activity and Sedentary behavior (ICAPS). Presence of a TV set in the bedroom (TV_bedroom) and leisure activities were obtained by questionnaire. There was annual assessment of BMI, waist circumference, and body fat by bioimpedance. Results: In boys but not girls, baseline TV_bedroom was associated with higher TV/video viewing over time [odds ratio (OR) of high TV/video = 1.87; 95% confidence interval, 1.2 to 2.8] and less no‐sport club participation (OR = 0.59; 95% confidence interval, 0.35 to 1.0). Both boys and girls with baseline TV_bedroom had lower reading time (p < 0.0001 in boys; p = 0.04 in girls), while PA did not differ according to TV_bedroom for boys or for girls. For boys only, baseline TV_bedroom was associated with higher BMI (mean BMI over time 20.5 ± 0.5 vs. 19.0 ± 0.5 kg/m²; p = 0.001), waist circumference (70.9 ± 0.9 vs. 67.2 ± 0.8 cm; p < 0.001), and body fat (15.9 ± 0.9% vs. 13.5 ± 0.9%; p < 0.001), without interaction with time. These relationships remained significant after adjustment for socioeconomic status. TV/video viewing explained 26%, 42%, and 36% of the relationships of TV_bedroom with BMI, waist circumference, and body fat, respectively, while addition of other leisure activities in the models only marginally reduced the effects. Discussion: These results suggest the importance of keeping TV out of an adolescent's bedroom from an obesity prevention perspective but show gender differences.     

Association Between Body Fat Response to Exercise Training and Multilocus ADR Genotypes

Objectives : To examine the contribution of adrenergic receptor (ADR) gene polymorphisms and their gene‐gene interactions to the variability of exercise training‐induced body fat response. Research Methods and Procedures : This was an intervention study that used a volunteer sample of 70 healthy, sedentary men (n = 29) and postmenopausal women (n = 41) 50 to 75 years of age, with a BMI ≤37 kg/m², from the Washington, DC, metropolitan area. Participants completed 6 weeks of dietary stabilization (American Heart Association diet) before 24 weeks of supervised aerobic exercise training. Diet was maintained throughout the intervention. Change in percent total body fat, percent trunk fat, and fat mass by DXA in ADR genotype groups (Glu¹²/Glu⁹ α2b‐ADR, Trp64Arg β3‐ADR, and Gln27Glu β2‐ADR) at baseline and after 24 weeks of aerobic exercise training was measured. Results : In multivariate analysis (covariates: age, gender, and baseline value of phenotype), best fit models for percent total body and trunk fat response to exercise training retained main effects of all three ADR gene loci and the effects of each gene‐gene interaction (p = 0.009 and 0.003, respectively). Similarly, there was a trend for the fat mass response model (p = 0.03). The combined genetic factors explained 17.5% of the overall model variability for percent total body fat, 22% for percent trunk fat, and 10% for fat mass. Discussion : The body fat response to exercise training in older adults is associated with the combined effects of the Glu¹²/Glu⁹ α2b‐, Trp64Arg β3‐, and Gln27Glu β2‐ADR gene variants and their gene‐gene interactions.     

Allosteric effects of atropine and carbachol on the activity of α<Subscript>2</Subscript>-adrenoceptors in rat brain cortex membranes

Activation and inhibition of muscarinic cholinoceptors by atropine and carbachol are shown to exert allosteric effects on the binding of specific nonselective α₂-adrenoceptor antagonist [³H]RX821002 in rat brain cortex membranes. The ligand-receptor interaction for α₂-adrenoceptors corresponded to the model suggesting the presence of one homogeneous pool of receptors with two specific binding sites. The parameters of the [³H]RX821002 binding were as follows: [³H]RX821002 -K _d = 1.94 ± 0.08 nM, B _max = 13.4 ± 1.8 fmol/mg protein, n = 2. The inhibition of muscarinic cholinoceptors by atropine induced an increase of affinity (K _d = 1.36 ± 0.12 nM) and a decrease of the α2-adrenoceptor density (B _max = 10.18 ± 0.48 fmol/mg protein). The muscarinic cholinoceptor agonist carbachol induced an increase of the affinity (K _d = 1.56 ± 0.05 nM) and quantity of binding sites (B _max = 16.61 ± 0.29 fmol/mg protein). As a result, under the influence of atropine and carbachol, the efficiency of binding (E = B _max/2K _d) increased from 3.50 ± 0.40 to 5.60 ± 0.79 and 6.86 ± 0.20 fmol/mg protein/nM, respectively. The data suggest that α₂-adrenoceptors exist in rat brain cortex as homodimers.     

Binding of synthetic peptide TPLVTLFK to nonopioid beta‐endorphin receptor on rat brain membranes

The synthetic peptide TPLVTLFK corresponding to the sequence 12–19 of β‐endorphin (referred to as octarphin) was found to bind to high‐affinity naloxone‐insensitive binding sites on membranes isolated from the rat brain cortex (K_d = 2.6 ± 0.2 nM ). The binding specificity study revealed that these binding sites were insensitive not only to naloxone but also to α‐endorphin, γ‐endorphin, [Met⁵]enkephalin, and [Leu⁵]enkephalin, as well. The [³H]octarphin specific binding with brain membranes was inhibited by unlabeled β‐endorphin (K_i = 2.4 ± 0.2 nM ) and a selective agonist of nonopioid β‐endorphin receptor decapeptide immunorphin SLTCLVKGFY (K_i = 2.9 ± 0.2 nM ). At the same time, unlabeled octarphin completely (by 100%) inhibited the specific binding of [³H]immunorphin with membranes (K_i = 2.8 ± 0.2 nM ). Thus, octarphin binds with a high affinity and specificity to nonopioid receptor of β‐endorphin on rat brain cortex membranes. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Effect of exercise training at different intensities on fat metabolism of obese men.

The present study investigated the effect of exercise training at different intensities on fat oxidation in obese men. Twenty-four healthy male obese subjects were randomly divided in either a low- [40% maximal oxygen consumption (VO(2 max))] or high-intensity exercise training program (70% VO(2 max)) for 12 wk, or a non-exercising control group. Before and after the intervention, measurements of fat metabolism at rest and during exercise were performed by using indirect calorimetry, [U-(13)C]palmitate, and [1,2-(13)C]acetate. Furthermore, body composition and maximal aerobic capacity were measured. Total fat oxidation did not change at rest in any group. During exercise, after low-intensity exercise training, fat oxidation was increased by 40% (P < 0.05) because of an increased non-plasma fatty acid oxidation (P < 0.05). High-intensity exercise training did not affect total fat oxidation during exercise. Changes in fat oxidation were not significantly different among groups. It was concluded that low-intensity exercise training in obese subjects seemed to increase fat oxidation during exercise but not at rest. No effect of high-intensity exercise training on fat oxidation could be shown.     

MC4R Variant Is Associated With BMI but Not Response to Resistance Training in Young Females

Recently, a genome‐wide association study (GWAS) that identified eight single‐nucleotide polymorphisms (SNPs) associated with BMI highlighted a possible neuronal influence on the development of obesity. We hypothesized these SNPs would govern the response of BMI and subcutaneous fat to resistance training in young individuals (age = 24 years). We genotyped the eight GWAS‐identified SNPs in the article by Willer et al. in a cohort (n = 796) that undertook a 12‐week resistance‐training program. Females with a copy of the rare allele (C) for rs17782313 (MC4R) had significantly higher BMIs (CC/CT: n = 174; 24.70 ± 0.33 kg/m², TT: n = 278; 23.41 ± 0.26 kg/m², P = 0.002), and the SNP explained 1.9% of overall variation in BMI. Males with a copy of the rare allele (T) for rs6548238 (TMEM18) had lower amounts of subcutaneous fat pretraining (CT/TT: n = 65; 156,534 ± 7,415 mm³, CC: n = 136; 177,825 ± 5,139 mm³, P = 0.019) and males with a copy of the rare allele (A) for rs9939609 (FTO) lost a significant amount of subcutaneous fat with exercise (AT/AA: n = 83; ?798.35 ± 2,624.30 mm³, TT: n = 47; 9,435.23 ± 3,494.44 mm³, P = 0.021). Females with a copy of the G allele for a missense variant in the SH2B1 (rs7498665) was associated with less change of subcutaneous fat volume with exercise (AG/GG: n = 191; 9,813 ± 2,250 mm³ vs. AA: n = 126; 770 ± 2,772 mm³; P = 0.011). These data support the original finding that there is an association between measures of obesity and a variant near the MC4R gene and extends these results to a younger population and implicates FTO, TMEM18, and SH2B1 polymorphisms in subcutaneous fat regulation.     

Glomerular thromboxane A2/prostaglandin H2 receptors: characterization and effect of adriamycin-induced nephrotic syndrome

We have characterized the thromboxane (TX) A₂/prostaglandin (PG) H₂ receptor in glomeruli isolated from the rat using the agonist radioligand [¹²⁵I]-BPO. Binding of [¹²⁵]-BOP was highly specific, stereoselective, and to a single class of high affinity binding sites (K_d = 1/16 ± 0.22 nM and B_max = 348 ± 32 fol/mg protein; n = 6). Binding of [¹²⁵I]-BOP was competed for by the agonist ONO11113 (K_d = 50.8 ± 8.0 nM; n = 4) and the antagonists SQ29548 (K_d = 15.8 ± 1.0 nM; n = 3), L657925 (K_d = 12.1 ± 2.2 nM; n = 3) and L65796 (K_d = 1642 ± 135 nM; n = 3). I-BOP also produced a TXA₂/PGH₂ receptor-mediated rise in [CA²⁺]_i in isolated glomeruli In adriamycin-induced nephrotic syndrome in the rat, the development of proteinuria is reported to be dependent on increased renal TXA₂ production. We therefore examined whether or not changes in glomerular TXA₂/PGH₂ receptors occur between control and nephrotic rats. No changes in expression of affinity of either glomerular or platelet TXA₂/PGH₂ receptors were observed. K_d and B_max values for isolated isolated glomeruli were 1.45 ± 0.24 nM and 406 ± 72 fmol/gm for controls and 1.22 ± 0.25 nM and 321 ± 62 fmol/gm for nephrotic rats (n = 6).