Exercise-induced oxidative stress in overweight adolescent girls: roles of basal insulin resistance and inflammation and oxygen overconsumption.

in International Journal of Obesity & Related Metabolic Disorders (2009), 33(4), 447-55

HYPOTHESIS: Basal insulin resistance (IR) and inflammation exacerbate post-exercise oxidative stress (OS) in overweight adolescent girls. DESIGN: Cross-sectional study, effect of incremental ergocycle ... [more ▼]

HYPOTHESIS: Basal insulin resistance (IR) and inflammation exacerbate post-exercise oxidative stress (OS) in overweight adolescent girls. DESIGN: Cross-sectional study, effect of incremental ergocycle exercise until exhaustion on OS markers. PARTICIPANTS: Normal-weight (control) (n=17, body mass index (BMI): 20-24.2 kg/m(2)) and overweight adolescent girls (n=29, BMI: 24.1-36.6 kg/m(2)). MEASUREMENTS: Dietary measurement, physical activity assessment (validated questionnaires), fat distribution parameters (by dual-energy X-ray absorptiometry and anthropometry) and maximal oxygen consumption (VO2peak). Blood assays include the following: (1) at fasting state: blood cell count, lipid profile, and IR parameters (leptin/adiponectin ratio (L/A), homeostasis model assessment of IR, insulin/glucose ratio; (2) before exercise: inflammation and OS markers (interleukin-6 (IL-6), C-reactive protein (CRP), myeloperoxidase (MPO), reduced glutathione/oxidized glutathione ratio (GSH/GSSG), 15 F(2)alpha-isoprostanes (F(2)-Isop), lipid hydroperoxides (ROOH), oxidized low-density lipoprotein (ox-LDL)) and antioxidant status (superoxide dismutase (SOD), glutathione peroxidase (GPX), vitamin C, alpha-tocopherol and beta-carotene); and (3) after exercise: inflammation and OS markers. RESULTS: At rest, overweight girls had a deteriorated lipid profile and significantly higher values of IR parameters and inflammation markers, compared with the control girls. These alterations were associated with a moderate rest OS state (lower GSH/GSSG ratio, alpha-tocopherol/total cholesterol (TC) ratio and GPX activity). In absolute values, overweight girls exhibited higher peak power output and oxygen consumption (VO2peak), compared with the control girls. Exercise exacerbated OS only in the overweight group (significant increase in F(2)-Isop, ROOH and MPO). As hypothesized, basal IR and inflammation state were correlated with the post-exercise OS. However, the adjustment of F(2)-Isop, ROOH and MPO variation per exercise VO(2) variation canceled the intergroup differences. CONCLUSION: In overweight adolescent girls, the main factors of OS, after incremental exhaustive exercise, are not the basal IR and inflammation states, but oxygen overconsumption. [less ▲]

The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study.

in International Journal of Obesity & Related Metabolic Disorders (2001), 25(11), 1713-21

OBJECTIVE: Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients. DESIGN: A 24 week multicentre, double-blind ... [more ▼]

OBJECTIVE: Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients. DESIGN: A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (-600 kcal/day; < or =30% of calories as fat)), 294 patients were submitted to the hypocaloric diet and randomly assigned to either orlistat 120 mg or placebo three times daily. Patients who completed the double-blind study (n=255) were eligible for participation in a subsequent 24 week open-label orlistat extension phase. SUBJECTS: Patients with body mass index (BMI) 27-40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1-6.7 mmol/l). MEASUREMENTS: Efficacy assessments included weight loss, lipid levels, other cardiovascular risk factors and anthropometric parameters. Safety assessments. RESULTS: Weight loss during run-in was similar in both groups. After randomization, orlistat-treated patients lost significantly more weight than placebo recipients: mean percentage weight loss from start of run-in to week 24 was-6.8% in the orlistat group and -3.8% in the placebo group (P<0.001). Moreover, more patients in the orlistat group than in the placebo group achieved clinically meaningful weight loss of > or =5% (64 vs 39%) or > or =10% (23 vs 13%) at week 24. Treatment with orlistat was associated with significantly greater changes in total cholesterol (-11.9% vs -4.0%; P<0.001) and LDL-C (-17.6 vs -7.6%; P<0.001). For any category of weight loss during the double-blind treatment period, change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients, indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction (P<0.001). Adjunction of orlistat during the extension phase in patients who initially received placebo induced a further decrease in weight, total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo, with the exception of a higher incidence of gastrointestinal events (> or =1 event in 64 vs 38% of patients). CONCLUSION: Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia. [less ▲]

Pharmacological treatment of obesity: present status.

in International Journal of Obesity & Related Metabolic Disorders (1999), 23 Suppl 1

OBJECTIVE: Obesity poses a serious health hazard and its treatment is often disappointing. This review describes the present status of pharmacological treatment of obesity in man. DESIGN: Obesity ... [more ▼]

OBJECTIVE: Obesity poses a serious health hazard and its treatment is often disappointing. This review describes the present status of pharmacological treatment of obesity in man. DESIGN: Obesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. The mode of action, efficacy and safety of each approach will be briefly discussed. RESULTS: All of the pharmacological possibilities have potential activities, but also serious limitations. While current anti-obesity pharmacotherapy essentially uses centrally-acting anorectic drugs, severe side-effects (more particularly pulmonary hypertension and valvular heart disease) have been reported, leading to the withdrawal of licensed fenfluramine and d-fenfluramine. New approaches have been recently proposed, such as sibutramine, an amine reuptake inhibitor which decreases food intake, and orlistat, an intestinal lipase inhibitor which decreases fat absorption. Obesity is a chronic disease and should be treated as such with reasonable expectations. Large-scale one-year placebo-controlled studies demonstrated that d-fenfluramine, sibutramine and orlistat significantly increased body weight loss by an average of 2-4 kg when compared to placebo and, more interestingly, multiplied by 2-3 the number of patients who succeeded in obtaining and maintaining a reduction of more than 10% of initial body weight. Interestingly, some of these compounds may also exert favourable effects on other vascular risk factors, independently of weight loss. CONCLUSIONS: Even if all anti-obesity pharmacological approaches can be helpful, they also have important limitations so that other strategies including either combined therapies or new drugs (peptides) are currently under investigation. [less ▲]

Influence of the A-->G (-3826) uncoupling protein-1 gene (UCP1) variant on the dynamics of body weight before and after gastroplasty in morbidly obese subjects.

in International Journal of Obesity & Related Metabolic Disorders (1998), 22(12), 1244-5

Glucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies.

in International Journal of Obesity & Related Metabolic Disorders (1995), 19 Suppl 3

Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for ... [more ▼]

Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after a marked weight loss and recovery of ideal body weight, arguing for acquired rather than inherited metabolic defects in presence of morbid obesity. If a sufficient weight reduction can not be obtained, pharmacological approaches may be considered to improve insulin resistance of obese subjects, especially those with impaired glucose tolerance or overt diabetes. [less ▲]

Relationships between metabolic clearance rate of insulin and body mass index in a female population ranging from anorexia nervosa to severe obesity.

in International Journal of Obesity & Related Metabolic Disorders (1994), 18(1), 47-53

Changes in the metabolic clearance rate of insulin (MCRI) have been described in several pathological conditions. Conflicting data suggest that they may be related to either body mass index (BMI) or body ... [more ▼]

Changes in the metabolic clearance rate of insulin (MCRI) have been described in several pathological conditions. Conflicting data suggest that they may be related to either body mass index (BMI) or body composition. This study aimed to investigate the relationship between the MCRI and BMI in an exclusively female population showing a wide range of BMI. For that purpose, hyperinsulinemic normoglycemic glucose clamps were performed in nine anorectic subjects (BMI: 14.5 +/- 0.8 kg/m2), 11 healthy volunteers (BMI: 20.3 +/- 0.5 kg/m2) and 12 obese patients (BMI: 33.0 +/- 0.9 kg/m2). To exclude any influence of the menstrual cycle on the MCRI, five healthy women underwent three tests at different days of the menstrual cycle: menstruation period, late follicular pre-ovulatory phase and luteal phase, in random order. The MCRI, which was quite reproducible in a given subject, was not significantly modified by the menstrual cycle. In the premenopausal female population studied, the mean (+/- s.e.m.) MCRI normalized for body weight (kg) were 35.4 +/- 3.4, 24.7 +/- 1.8 and 14.0 +/- 1.0 ml/kg/min (P < 0.01) for anorectic subjects, healthy volunteers and obese patients, respectively. These differences were maintained when the MCRI was normalized according to corporeal surface (m2) (1018 +/- 75, 859 +/- 67, 638 +/- 40 ml/m2/min, P < 0.01) or lean body mass (kg) (37.1 +/- 3.4, 32.6 +/- 2.7 and 24.1 +/- 0.5 ml/kgLBM/min, P < 0.01), but disappeared when MCRI was expressed per kg of ideal body weight (24.6 +/- 2.2, 24.6 +/- 2.1 and 22.4 +/- 1.4 ml/kgIBW/min, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Effect of protein-supplemented fasting on the fuel-hormone response to prolonged exercise in obese subjects.

in International Journal of Obesity & Related Metabolic Disorders (1983), 7(4), 327-37

This study aimed at investigating the influence of protein-supplemented fasting (PSF) on the tolerance and the fuel-hormone response to endurance exercise in the severely obese subject. For this purpose ... [more ▼]

This study aimed at investigating the influence of protein-supplemented fasting (PSF) on the tolerance and the fuel-hormone response to endurance exercise in the severely obese subject. For this purpose, eight obese men (27 +/- 2 yr, 182 +/- 7 per cent of ideal body weight) exercised on a horizontal treadmill (4 km/h) during 3 h before and after 13 d of PSF (Alburone, 70 g protein/day). Because of the 8.9 +/- 0.7 kg weight loss and the corresponding lower energy cost, exercise oxygen consumption decreased from 1.6 +/- 0.1 (before PSF) to 1.4 +/- 0.1 l/min (after PSF). In contrast, mean exercise heart rate was identical (119 +/- 5/min) in both conditions, resulting in a lower oxygen pulse after PSF. The mean respiratory quotient measured during exercise was lower after PSF (0.72 +/- 0.01 vs 0.75 +/- 0.01 2 P less than 0.05), thus demonstrating a higher fat utilization. This was supported by a higher exercise-induced plasma free fatty acid (FFA) mobilization after PSF (delta plasma FFA: + 675 +/- 101 vs + 376 +/- 121 mumol/l, 2 P less than 0.05). This metabolic adaptation mainly results from two mechanisms: a significantly lower plasma IRI at rest and during exercise after PSF (5.7 +/- 0.8 vs 11.4 +/- 1.4 microunits/ml, 2 P less than 0.001); and a lower basal blood glucose (4.2 +/- 0.2 vs 4.6 +/- 0.1 mmol/l) and an earlier decrease of glucose (30th vs 90th min) during exercise after PSF, suggesting a relative depletion of the carbohydrates stores. The lipolytic hormones (glucagon, epinephrine, norepinephrine, cortisol, growth hormone) did not significantly increase during exercise after PSF when compared to exercise before PSF; thus, their role in the enhanced FFA mobilization appears less important. Only two of our eight subjects were unable to achieve the third hour of exercise after PSF; however, no major clinical events or electrocardiographical disturbances were observed in any of the eight subjects. In conclusion, moderate exercise can be tolerated at least for 2 h during PSF when appropriate fluid, mineral and vitamin therapy is given. Under these conditions it induces a preferential utilization of fat-derived substrates and selectively augments fat mobilization which favors weight loss. For these reasons, moderate exercise can be recommended under strict medical supervision as part of all weight reduction therapy. [less ▲]

Hormonal and metabolic adaptation to protein-supplemented fasting in obese subjects.

in International Journal of Obesity & Related Metabolic Disorders (1982), 6(2), 165-74

Thirty hospitalized, severely obese patients (40 +/- 2 yr, 82 +/- 4 percent weight excess) were submitted to a 13-d protein-supplemented fast (PSF) with 70 g milk proteins/d (1.26 MJ or 300 kcal). The ... [more ▼]

Thirty hospitalized, severely obese patients (40 +/- 2 yr, 82 +/- 4 percent weight excess) were submitted to a 13-d protein-supplemented fast (PSF) with 70 g milk proteins/d (1.26 MJ or 300 kcal). The mean weight loss during PSF was 5.4 +/- 0.3 kg corresponding to 422 +/- 39 g/d. Comparison of the urinary nitrogen excretion with daily protein intake revealed that the nitrogen balance was equilibrated during PSF. Blood glucose decreased moderately but significantly during the whole PSF period whereas plasma insulin was only reduced during the first 9 d and tended to rise thereafter. Plasma FFA increased rapidly and remained elevated until the end of the study (+ 60 per cent); serum total cholesterol and plasma triglycerides showed a 26 and a 35 per cent decrease respectively. Basal plasma glucagon was slightly increased. Due to the low sodium intake (42 mmol/d) urinary sodium excretion dropped rapidly. Simultaneously both systolic (-13 mmHg) and diastolic (-7 mmHg) arterial blood pressure decreased significantly. The biological tolerance was good: metabolic acidosis was prevented with sodium bicarbonate, excessive rise in serum uric acid was corrected with allopurinol and a marked decrease in serum potassium was avoided with an appropriate dose of spironolactone. Twenty-six patients could be weighed 6 to 15 months after PSF: 12 showed a further weight reduction (6.6 +/- 1.6 kg) and seven a discrete weight gain (1.0 +/- 0.4 kg). Thus, PSF was well accepted and was profitable in 19 out of our 30 patients. It should be restricted to cases of severe and refractory obesity and performed under careful medical supervision. [less ▲]