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.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Obesity Affects Myocardial Vasoreactivity and Coronary Flow Response to Insulin

Objective: Obesity is associated with increased risk for cardiovascular diseases and peripheral endothelial dysfunction. We examined whether myocardial vasoreactivity and coronary‐flow response to insulin stimulation are altered in obesity. Research Methods and Procedures: Myocardial blood flow was quantitated in 10 obese men (body mass index, 33.6 ± 1.9 kg/m²) and 10 healthy matched non‐obese men (body mass index, 24.2 ± 1.9 kg/m²), using positron emission tomography and oxygen‐15‐labeled water. The measurements were performed basally and during adenosine infusion (140 μg/kg per minute), with or without simultaneous physiological (1 mU/kg per minute) and supraphysiological (5 mU/kg per minute) hyperinsulinemia. Results: Basal myocardial blood flow was not significantly different between obese and non‐obese subjects. Adenosine‐stimulated flow was blunted in obese (3.2 ± 0.6 mL/g per minute) when compared with non‐obese subjects (4.0 ± 1.1 mL/g per minute, p < 0.05). Simultaneous physiological hyperinsulinemia increased adenosine‐stimulated myocardial flow significantly in both groups (to 4.03 ± 1.24 and 4.85 ± 1.04 mL/g per minute in obese and non‐obese men, respectively; p < 0.05 vs. adenosine). Supraphysiological hyperinsulinemia further enhanced the adenosine‐stimulated flow in non‐obese subjects (to 5.56 ± 0.98 mL/g per minute; p < 0.05) but not in obese subjects. Discussion: Young obese, healthy men have reduced myocardial vasoreactivity, which may represent an early precursor of future coronary artery disease. Additionally, insulin‐induced enhancement of myocardial blood flow is blunted in obesity. Thus, endothelial dysfunction seems to also characterize myocardial vasculature of obese subjects.     

Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.     

The Val103Ile Polymorphism of Melanocortin‐4 Receptor Regulates Energy Expenditure and Weight Gain

Objective: The melanocortin‐4 receptor (MC4R) regulates energy intake. On the basis of animal studies, it may also regulate energy expenditure. Research Methods and Procedures: The effect of the Val103Ile polymorphism of the MC4R gene on energy metabolism was studied in 229 middle‐aged nondiabetic subjects (Group 1, age 51.2 ± 9.8 years, BMI 26.8 ± 4.5 kg/m²) and on weight gain in 1013 elderly subjects (Group 2, age 69.9 ± 2.9 years, BMI 27.4 ± 4.1 kg/m²) during a 3.5‐year follow‐up study. In Group 1, insulin sensitivity, energy expenditure, and substrate oxidation were measured with the hyperinsulinemic euglycemic clamp combined with indirect calorimetry. Results: In Group 1, the Val103Ile genotype was associated with high rates of energy expenditure (63.42 ± 13.40 in eight subjects with the Val103Ile genotype vs. 59.86 ± 7.33 J/kg per minute in 221 subjects with the Val103Val genotype, p = 0.007), high rates of glucose oxidation (8.90 ± 6.15 vs. 6.07 ± 4.38 μmol/kg per minute, p = 0.020), and low levels of free fatty acids (0.45 ± 0.18 vs. 0.56 ± 0.23 mM, p = 0.029) in the fasting state, and with high rates of glucose oxidation during the clamp (18.88 ± 4.63 vs. 17.60 ± 3.24 μmol/kg per minute, p = 0.031). In Group 2, the 103Ile allele was associated with an increase in weight gain during the follow‐up (0.78 ± 3.98 vs. ?0.82 ± 3.98 kg, p = 0.038). Discussion: The Val103Ile polymorphism of the MC4R gene is associated with energy expenditure in humans. Furthermore, it may associate with glucose oxidation, free fatty acid levels, and weight gain.     

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.     

Normal Insulin Sensitivity in Lean Offspring of Obese Parents

Objective: Offspring of diabetic or hypertensive patients are insulin resistant at a prediabetic/prehypertensive stage. We tested the hypothesis that insulin action may be impaired in the offspring of obese nondiabetic parents. Research Methods and Procedures: Twenty‐one lean offspring of nonobese subjects [(OL) 22 ± 3 years of age] were matched to 23 lean offspring of obese subjects (OOb) by gender distribution, age, BMI, and waist circumference. Anthropometry, oral glucose tolerance, in vivo insulin sensitivity [by a euglycemic insulin clamp (6 pmol/min per kilogram_FFM; where FFM represents fat‐free mass)], and thermogenesis (by indirect calorimetry) were measured in each subject. The study subjects were from a population of 267 nuclear families (one offspring and both his/her parents) in which there was statistically significant (χ² = 30.2, p = 0.001) concordance of BMI between parents and offspring. Results: In comparing OOb with OL, no statistically significant difference or trend toward a difference was detected in fasting plasma glucose and insulin concentrations, glucose and insulin responses to oral glucose, insulin sensitivity [metabolism value = 45 ± 12 (OOb) vs. 47 ± 17 μmol/min per kilogram_FFM (OL)], insulin‐induced inhibition of protein and lipid oxidation, stimulation of glucose oxidation and nonoxidative glucose disposal, respiratory quotient, resting energy expenditure, and glucose‐induced thermogenesis. Discussion: The metabolic similarity between lean offspring of obese parents and those of nonobese parents suggests that insulin resistance and its correlates are not co‐inherited with the predisposition to develop obesity.     

Differences in daily energy expenditure in lean and obese women: the role of posture allocation

Objective: A low resting metabolic rate (RMR) is considered a risk factor for weight gain and obesity; however, due to the greater fat‐free mass (FFM) found in obesity, detecting an impairment in RMR is difficult. The purposes of this study were to determine the RMR in lean and obese women controlling for FFM and investigate activity energy expenditure (AEE) and daily activity patterns in the two groups. Methods and Procedures: Twenty healthy, non‐smoking, pre‐menopausal women (10 lean and 10 obese) participated in this 14‐day observational study on free‐living energy balance. RMR was measured by indirect calorimetry; AEE and total energy expenditure (TEE) were calculated using doubly labeled water (DLW), and activity patterns were investigated using monitors. Body composition including FFM and fat mass (FM) was measured by dual energy X‐ray absorptiometry (DXA). Results: RMR was similar in the obese vs. lean women (1601 ± 109 vs. 1505 ± 109 kcal/day, respectively, P = 0.12, adjusting for FFM and FM). Obese women sat 2.5 h more each day (12.7 ± 3.2 h vs. 10.1 ± 2.0 h, P < 0.05), stood 2 h less (2.7 ± 1.0 h vs. 4.7 ± 2.2 h, P = 0.02) and spent half as much time in activity than lean women (2.6 ± 1.5 h vs. 5.4 ± 1.9 h, P = 0.002). Discussion: RMR was not lower in the obese women; however, they were more sedentary and expended less energy in activity than the lean women. If the obese women adopted the activity patterns of the lean women, including a modification of posture allocation, an additional 300 kcal could be expended every day.     

High Serum Leptin Is Associated with Attenuated Coronary Vasoreactivity

Objective: Hyperleptinemia, a hallmark of obesity, appears to be a risk factor for coronary artery disease. However, although leptin is a vasoactive hormone, no studies addressing leptin's effect on coronary perfusion have been performed. We examined the association between circulating leptin concentration and coronary vasoreactivity in young obese and nonobese males. Research Methods and Procedures: Myocardial blood flow was quantitated in 10 obese men (age 31 ± 7 years, BMI 34 ± 2 kg/m²) and 10 healthy matched nonobese men (age 33 ± 8 years, BMI 24 ± 2 kg/m²) using positron emission tomography and O‐15‐water. The measurements were performed basally and during adenosine infusion (140 μg/kg per minute). Results: Serum leptin was significantly higher in obese than nonobese subjects (10.3 ± 5.6 vs. 4.3 ± 2.5 ng/mL, p < 0.01). Basal myocardial blood flow was not significantly different between obese and nonobese subjects. Adenosine‐stimulated flow was blunted in obese (3.2 ± 0.6 mL/g per minute) when compared with nonobese subjects (4.0 ± 1.1 mL/g per minute, p < 0.05). Serum leptin concentration was inversely associated with adenosine‐stimulated flow in study subjects (r = ?0.50, p < 0.05). This association was no longer observed after adjustment for obesity and/or hyperinsulinemia. Discussion: Hyperleptinemia and reduced coronary vasoreactivity occur concomitantly in young obese but otherwise healthy men. Moreover, the adenosine‐stimulated myocardial flow is inversely related to prevailing concentration of serum leptin. Although this relationship appears to be explained by obesity and/or hyperinsulinemia, leptin might have a role in regulation of myocardial blood supply.     

Dose-dependent effects of training and detraining on weight in 6406 runners during 7.4 years

Objective: Prior randomized and non‐randomized training studies have failed to establish a dose‐response relationship between vigorous exercise and weight loss; this failure may be due, in part, to their short durations and small sample sizes. The objectives of this study were to determine whether exercise reduces body weight and to examine the dose‐response relationships between changes in exercise and changes in total and regional adiposity. Research Methods and Procedures: This was a large prospective study of 3973 men and 1444 women who quit running (detraining), 270 men and 146 women who started running (training), and 420 men and 153 women who remained sedentary during 7.4 years of follow‐up. The outcomes measured were weekly running distance, body weight, BMI, body circumferences, and bra cup size. Results: There were significant inverse relationships between the changes in the amount of vigorous exercise (km/wk run) and the changes in weight and BMI in men (slope ± standard error: ?0.039 ± 0.005 kg/km per week and ?0.012 ± 0.002 kg/m² per km/wk, respectively) and in older women (?0.060 ± 0.018 kg/km per week and ?0.022 ± 0.007 kg/m² per km/wk) who quit running, and in initially sedentary men (?0.098 ± 0.017 kg/km per week and ?0.032 ± 0.005 kg/m² per km/wk) and women (?0.062 ± 0.023 kg/km per week and ?0.021 ± 0.008 kg/m² per km/wk) who started running. Changes in waist circumference, an indicator of intra‐abdominal fat, were also inversely related to changes in running distance in men who quit (?0.026 ± 0.005 cm/km per week) or started running (?0.078 ± 0.017 cm/km per week). Discussion: The initiation of vigorous exercise and its cessation decrease and increase, respectively, body weight and intra‐abdominal fat, and these changes are proportional to the change in exercise dose.     

Relationship Between Body Fat Mass and Free Fatty Acid Kinetics in Men and Women

An increased release of free fatty acids (FFAs) into plasma likely contributes to the metabolic complications associated with obesity. However, the relationship between body fat and FFA metabolism is unclear because of conflicting results from different studies. The goal of our study was to determine the inter‐relationships between body fat, sex, and plasma FFA kinetics. We determined FFA rate of appearance (R_a) in plasma, by using stable isotopically labeled tracer techniques, during basal conditions in 106 lean, overweight, and obese, nondiabetic subjects (43 men and 63 women who had 7.0–56.0% body fat). Correlation analyses demonstrated: (i) no differences between men and women in the relationship between fat mass (FM) and total FFA R_a (µmol/min); (ii) total FFA R_a increased linearly with increasing FM (r = 0.652, P < 0.001); (iii) FFA R_a per kg FM decreased in a curvilinear fashion with increasing FM (r = ?0.806; P < 0.001); (iv) FFA R_a in relationship to fat‐free mass (FFM) was greater in obese than lean subjects and greater in women than in men; and (v) abdominal fat itself was not an important determinant of total FFA R_a. We conclude that total body fat, not regional fat distribution or sex, is an important modulator of the rate of FFA release into plasma. Although increased adiposity is associated with a decrease in fatty acid release in relationship to FM, this downregulation is unable to completely compensate for the increase in FM, so total FFA R_a and FFA R_a with respect to FFM are greater in women than in men and in obese than in lean subjects.     

Excess body fat in men decreases plasma fatty acid availability and oxidation during endurance exercise

The effect of relative body fat mass on exercise-induced stimulation of lipolysis and fatty acid oxidation was evaluated in 15 untrained men (5 lean, 5 overweight, and 5 obese with body mass indexes of 21 +/- 1, 27 +/- 1, and 34 +/- 1 kg/m2, respectively, and %body fat ranging from 12 to 32%). Palmitate and glycerol kinetics and substrate oxidation were assessed during 90 min of cycling at 50% peak aerobic capacity (VO2 peak) by use of stable isotope-labeled tracer infusion and indirect calorimetry. An inverse relationship was found between %body fat and exercise-induced increase in glycerol appearance rate relative to fat mass (r2 = 0.74; P < 0.01). The increase in total fatty acid uptake during exercise [(micromol/kg fat-free mass) x 90 min] was approximately 50% smaller in obese (181 +/- 70; P < 0.05) and approximately 35% smaller in overweight (230 +/- 71; P < 0.05) than in lean (354 +/- 34) men. The percentage of total fatty acid oxidation derived from systemic plasma fatty acids decreased with increasing body fat, from 49 +/- 3% in lean to 39 +/- 4% in obese men (P < 0.05); conversely, the percentage of nonsystemic fatty acids, presumably derived from intramuscular and possibly plasma triglycerides, increased with increasing body fat (P < 0.05). We conclude that the lipolytic response to exercise decreases with increasing adiposity. The blunted increase in lipolytic rate in overweight and obese men compared with lean men limits the availability of plasma fatty acids as a fuel during exercise. However, the rate of total fat oxidation was similar in all groups because of a compensatory increase in the oxidation of nonsystemic fatty acids.     

A Weight Reduction Program Preserves Fat‐Free Mass but Not Metabolic Rate in Obese Adolescents

Objective: To determine the effects of a multidisciplinary weight reduction program on body composition and energy expenditure (EE) in severely obese adolescents. Research Methods and Procedures: Twenty‐six severely obese adolescents, 12 to 16 years old [mean BMI: 33.9 kg/m²; 41.5% fat mass (FM)] followed a 9‐month weight reduction program including moderate energy restriction and progressive endurance and resistance training. Body composition was assessed by DXA, basal metabolic rate by indirect calorimetry, and EE by whole‐body indirect calorimetry with the same activity program over 36‐hour periods before starting and 9 months after the weight reduction period. Results: Adolescents gained (least‐square mean ± SE) 2.9 ± 0.2 cm in height, lost 16.9 ± 1.3 kg body weight (BW), 15.2 ± 0.9 kg FM, and 1.8 ± 0.5 kg fat‐free mass (FFM) (p < 0.001). Basal metabolic rate, sleeping, sedentary, and daily EE were 8% to 14% lower 9 months after starting (p < 0.001) and still 6% to 12% lower after adjustment for FFM (p < 0.05). Energy cost of walking decreased by 22% (p < 0.001). The reduction in heart rate during sleep and sedentary activities (?10 to ?13 beats/min), and walking (?20 to ?25 beats/min) (p < 0.001) resulted from both the decrease in BW and physical training. Discussion: A weight reduction program combining moderate energy restriction and physical training in severely obese adolescents resulted in great BW and FM losses and improvement of cardiovascular fitness but did not prevent the decline in EE even after adjustment for FFM.     

A 12‐Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese,Hispanic Adolescents

The rise in obesity‐related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized that a 12‐week controlled aerobic exercise program without weight loss reduces visceral, hepatic, and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents. Twenty‐nine postpubertal (Tanner stage IV and V), Hispanic adolescents, 15 obese (7 boys, 8 girls; 15.6 ± 0.4 years; 33.7 ± 1.1 kg/m²; 38.3 ± 1.5% body fat) and 14 lean (10 boys, 4 girls; 15.1 ± 0.3 years; 20.6 ± 0.8 kg/m²; 18.9 ± 1.5% body fat), completed a 12‐week aerobic exercise program (4 × 30 min/week at ≥70% of peak oxygen consumption (VO₂peak)). Measurements of cardiovascular fitness, visceral, hepatic, and intramyocellular fat content (magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS)), and insulin resistance were obtained at baseline and postexercise. In both groups, fitness increased (obese: 13 ± 2%, lean: 16 ± 4%; both P < 0.01). In obese participants, intramyocellular fat remained unchanged, whereas hepatic fat content decreased from 8.9 ± 3.2 to 5.6 ± 1.8%; P < 0.05 and visceral fat content from 54.7 ± 6.0 to 49.6 ± 5.5 cm²; P < 0.05. Insulin resistance decreased indicated by decreased fasting insulin (21.8 ± 2.7 to 18.2 ± 2.4 µU/ml; P < 0.01) and homeostasis model assessment of insulin resistance (HOMA_IR) (4.9 ± 0.7 to 4.1 ± 0.6; P < 0.01). The decrease in visceral fat correlated with the decrease in fasting insulin (R² = 0.40; P < 0.05). No significant changes were observed in any parameter in lean participants except a small increase in lean body mass (LBM). Thus, a controlled aerobic exercise program, without weight loss, reduced hepatic and visceral fat accumulation, and decreased insulin resistance in obese adolescents.     

Effects of Insulin on Ketogenesis Following Fasting in Lean and Obese Men

The ketone bodies (KBs) D‐3‐hydroxybutyrate (D‐3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance. The dose–response relationship between insulin and KBs was demonstrated to be shifted to the right in type 2 diabetes patients. However, KB levels have also been reported to be decreased in obesity. We investigated the metabolic adaptation to fasting with respect to glucose and KB metabolism in lean and obese men without type 2 diabetes using stable glucose and D‐3HB isotopes in a two‐step pancreatic clamp after 38 h of fasting. We found that D‐3HB fluxes in the basal state were higher in lean compared to obese men: 15.2 (10.7–27.1) vs. 7.0 (3.5–15.1) µmol/kg lean body mass (LBM)·min, respectively, P < 0.01. No differences were found in KB fluxes between lean and obese volunteers during the pancreatic clamp (step 1: 6.9 (1.8–12.0) vs. 7.4 (4.2–17.8) µmol/kg LBM·min, respectively; and step 2: 2.9 (0–7.2) vs. 3.4 (0.85–18.7) µmol/kg LBM·min, respectively), despite similar plasma insulin levels. Meanwhile, peripheral glucose uptake was higher in lean compared to obese men (step 1: 15.2 (12.3–25.6) vs. 14.7 (11.9–22.7) µmol/kg LBM·min, respectively, P ≤ 0.05; and step 2: 12.5 (7.0–17.3) vs. 10.8 (5.2–15.0) µmol/kg LBM·min, respectively, P ≤ 0.01). These data show that obese subjects who display insulin resistance on insulin‐mediated peripheral glucose uptake have the same sensitivity for the insulin‐mediated suppression of ketogenesis. This implies differential insulin sensitivity of intermediary metabolism in obesity.     

Lipid oxidation according to intensity and exercise duration in overweight men and women

Objective: Our objective was to compare the effect of different exercise intensities on lipid oxidation in overweight men and women. Research Methods and Procedures: Nine young, healthy, overweight men and women were studied (age, 31.4 ± 2.3 and 26.7 ± 2.1 years; BMI, 27.9 ± 0.4 and 27.2 ± 0.5; for men and women, respectively). On one study day, the subjects first performed 30 minutes of cycling exercise at 30% of their maximal oxygen uptake (Vo _2max; E1 session), followed by 30 minutes of exercise at 50% Vo _2max (E2 session). On a second study day, a similar E1 session was followed by 30 minutes of exercise at 70% Vo _2max (E3 session). From the gas exchange measurements, the respiratory exchange ratio (RER) and the fat oxidation rate (FOR) were calculated. Plasma concentrations of glycerol and non‐esterified fatty acids (NEFAs) were assayed. Results: RER was significantly lower for women during only the E1 session. For both sexes, RER decreased over time during the E2 and E3 sessions. During the E1 session, the FOR per kilogram of lean mass (LM) was higher among women, and it did not change over time despite an increase in plasma NEFAs. FOR per kilogram of LM was higher during the E2 exercise for both sexes. During E2 and E3 sessions, as the exercise time was prolonged, the FOR/kg LM increased simultaneously with the increase in the plasma glycerol. Discussion: Lipid oxidation during exercise is optimized for moderate and lengthy exercise. The enhancement of lipid oxidation occurring over time during moderate‐ and high‐intensity exercises could be, in part, linked to the improvement of lipid mobilization. This fact is discussed to shed light on exercise modalities as a tool for the management of overweight.     

Comparison of three bioelectrical impedance methods with DXA in overweight and obese men

Objective: To compare bioelectrical impedance analysis (BIA) of body composition using three different methods against DXA in overweight and obese men. Research Methods and Procedures: Forty‐three healthy overweight or obese men (ages 25 to 60 years; BMI, 28 to 43 kg/m²) underwent BIA assessment of body composition using the ImpediMed SFB7 (version 6; ImpediMed, Ltd., Eight Mile Plains, Queensland, Australia) in multifrequency mode (Imp‐MF) and DF50 single‐frequency mode (Imp‐SF) and the Tanita UltimateScale (Tanita Corp., Tokyo, Japan). Validity was assessed by comparison against DXA using linear regression and limits of agreement analysis. Results: All three BIA methods showed good relative agreement with DXA [Imp‐MF: fat mass (FM), r² = 0.81; fat‐free mass (FFM), r² = 0.81; percentage body fat (BF%), r² = 0.69; Imp‐SF: FM, r² = 0.65; FFM, r² = 0.76; BF%, r² = 0.40; Tanita: BF%, r² = 0.44; all p < 0.001]. Absolute agreement between DXA and Imp‐MF was poor, as indicated by a large bias and wide limits of agreement (bias, ±1.96 standard deviation; FM, ?6.6 ± 7.7 kg; FFM, 8.0 ± 7.1 kg; BF%, ?7.0 ± 6.6%). Imp‐SF and Tanita exhibited a smaller bias but wide limits of agreement (Imp‐SF: FM, ?1.1 ± 8.5 kg; FFM, 2.5 ± 7.9 kg; BF%, ?1.7 ± 7.3% Tanita: BF%, 1.2 ± 9.5%). Discussion: Compared with DXA, Imp‐MF produced large bias and wide limits of agreement, and its accuracy estimating body composition in overweight or obese men was poor. Imp‐SF and Tanita demonstrated little bias and may be useful for group comparisons, but their utility for assessment of body composition in individuals is limited.     

Physical Activity Levels Are Low in Free‐Living Adults with Chronic Paraplegia

Objectives: To compare physical activity levels (PALs) of free‐living adults with chronic paraplegia with World Health Organization recommendations and to compare energy expenditure between persons with complete vs. incomplete paraplegia. Research Methods and Procedures: Twenty‐seven euthyroid adults (17 men and 10 women) with paraplegia (12.5 ± 9.5 years since onset; 17 with complete lesions and 10 with incomplete lesions) participated in this cross‐sectional study. Resting metabolic rate was measured by indirect calorimetry and total daily energy expenditure (TDEE) by heart rate monitoring. PAL was calculated as TDEE/resting metabolic rate. Total body water was measured by deuterium dilution and fat‐free mass (FFM) and fat mass (FM) by calculation (FFM = total body water/0.732; FM = weight ? FFM). Obesity was defined using the following percentage FM cutoffs: men 18 to 40 years >22% and 41 to 60 years >25%; and women 18 to 40 years >35% and 41 to 60 years >38%. Results: Nineteen subjects (70.4%; 13 men and six women) were obese. Fifteen subjects (56%) engaged in structured physical activity 1.46 ± 0.85 times during the observation period for a mean of 49.4 ± 31.0 minutes per session. Despite this, mean PAL of the group was 1.56 ± 0.34, indicative of limited physical activity. TDEE was 24.6% lower in subjects with complete paraplegia (2072 ± 505 vs. 2582 ± 852 kcal/d, p = 0.0372). Discussion: PAL of the group was low, indicating that persons with paraplegia need to engage in increased frequency, intensity, and/or duration of structured physical activity to achieve a PAL ≥1.75 and, thereby, to offset sedentary activities of daily living.     

Influence of knee osteoarthritis on exercise capacity and quality of life in obese adults

Objective: The objective was to determine whether knee osteoarthritis (OA) reduces exercise ambulatory capacity and impairs quality of life (QOL) in obese individuals. Research Methods and Procedures: There were 56 subjects, with and without knee OA, who were obese. The subjects were evaluated with anthropometric measurements, a body composition assessment, maximal cardiopulmonary exercise test, 6‐minute walk test (6‐MWT), perceived exertion (RPE), self‐reported disability [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)], and the Medical Outcomes Study Short Form 36 (SF‐36). Results: VO_2peak was significantly higher in the controls when compared with the patients (mean ± standard deviation, 1.584 ± 0.23 L/kg per min vs. 0.986 ± 0.20 L/kg per min; p < 0.001). Obese subjects without knee OA walked a significantly longer distance in the 6‐MWT than obese patients with knee OA (p < 0.001). We also observed significant negative correlation between Vo ₂max and RPE, WOMAC pain and physical limitation, and bodily pain and general health domains of short‐form 36. Discussion: Knee OA reduces exercise and ambulatory capacity and impairs QOL in obese individuals. RPE, WOMAC pain, and SF‐36 items might provide information about exercise capacity in the obese subjects with knee OA. Our study confirms that exercise capacity and QOL might be improved by energetic and intensive treatment of pain resulting from knee OA.