Obesity Capacity Research Articles

Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity

Hepatic mitochondrial respiration is higher in steatosis, but lower in overt type 2 diabetes. We hypothesized that hepatic OXPHOS capacity increases with a greater degree of insulin resistance in obesity, independent of other metabolic diseases. We analysed 65 humans without diabetes (BMI 50±7 kg/m2, HbA1c 5.5±0.4%) undergoing bariatric surgery. MASLD stages were assessed by histology, whole-body insulin sensitivity (PREDIcted-M index) by oral glucose tolerance tests, and maximal ADP-stimulated mitochondrial OXPHOS capacity by high-resolution respirometry of liver samples. Prediabetes was present in 30 participants, and MASLD in 46 participants. Thereof, 25 had metabolic dysfunction-associated steatohepatitis (MASH), and seven had F2-F3 fibrosis. While simple regression did not detect an association of insulin sensitivity with hepatic OXPHOS capacity, interaction analyses revealed that the regression coefficient of OXPHOS capacity depended on fasting plasma glucose (FPG) and liver lipid content. Interestingly, the respective slopes were negative for FPG ≤100 mg/dl, but positive for FPG >100 mg/dl. Liver lipid content displayed similar behavior, with a threshold value of 24%. Post-challenge glycemia affected the association between insulin sensitivity and OXPHOS capacity normalized for citrate synthase activity. Presence of prediabetes affected hepatic insulin signaling, mitochondrial dynamics and fibrosis prevalence, while the presence of MASLD related to higher biomarkers of hepatic inflammation, cell damage and lipid peroxidation in people with normal glucose tolerance. Rising liver lipid contents and plasma glucose concentrations, even in the non-diabetic range, are associated with a progressive decline of hepatic mitochondrial adaptation in people with obesity and insulin resistance. CLINTRIALS. NCT01477957.

Impaired Capillary Recruitment Capacity in Obesity: A Subgroup Analysis of Prospective Observational Study on Anesthesia Effects.

BACKGROUND This subgroup analysis of prospective observational research, involving 71 participants, compared the effects of anesthesia on microvascular reactivity in obese vs lean individuals using near-infrared spectroscopy and vascular occlusion tests. The correlation between the body mass index (BMI) and microvascular reactivity under general anesthesia was also investigated. MATERIAL AND METHODS This study enrolled adult patients classified as American Society of Anesthesiologists physical status I or II, undergoing elective surgery under general anesthesia. The microcirculatory variables measured before (Tpre) and 30 min following the induction of anesthesia (Tpost) were as follows: baseline tissue oxygen saturation (StO₂), occlusion slope (∇occl), and recovery slope (∇recov). The patients were grouped according to their BMI (lean [BMI <25 kg/m²] vs obese [BMI ≥25 kg/m²]). Data are presented as medians and interquartile ranges. RESULTS There were 43 patients in the lean group and 28 in the obese group. At Tpre, baseline StO2, ∇occl, and ∇recov were not different between the 2 groups (P=0.860, 0.659, and 0.518, respectively). At Tpost, the baseline StO₂ and ∇occl were not different between the 2 groups (P=0.343 and 0.791); however, the ∇recov was lower in the obese group than in the lean group (3.245 [2.737, 3.977] vs 4.131 [3.491, 4.843], P=0.003). At Tpost, BMI showed a moderate correlation with ∇recov (correlation coefficient: -0.319, P=0.007). CONCLUSIONS In obese patients, capillary recruitment capacity during general anesthesia is compromised compared to lean patients.

Aerobic exercise capacity is normal in obesity with or without metabolic syndrome

BackgroundObesity might be a cause of limited aerobic exercise capacity. It is often associated with metabolic syndrome (MS) that includes cardiovascular comorbidities as arterial hypertension. Cardiopulmonary exercise testing (CPET) is the gold-standard to assess aerobic capacity and discriminate causes of dyspnea. AimTo evaluate aerobic capacity in obesity and if MS or hypertensive treatment impacts on the CPET profile. MethodsCPET of 146 obese patients, whom 33 and 31 were matched for MS and antihypertensive medication, were analyzed. VO2peak (mL/min/Kg) was reported in percentage of predicted value, or, divided by body weight, fat free mass (FFM) or body weight expected for a body mass index of 24 (BMI24). ResultsVO2peak (20,8 ± 4,4 mL/min/Kg) was normal when expressed in percentage predicted for obesity (111 ± 22%pred) or divided by FFM and weightBMI24 (33,6 ± 5,6 and 30,6 ± 6,2 respectively). The latter correlated better with maximal work rate (r = 0,7168, p < 0,001). Obese patients showed normal ventilatory efficiency (ventilation to carbon dioxide production slope: 28 ± 4), VO2 to work rate (10,2 ± 1,6 mLO2/Watt) and, slightly elevated heart rate to VO2 slope (4,0 ± 1,1 bpm/mL/min/Kg). Compared to normotensives, hypertensive medicated patients had higher blood pressure at anaerobic threshold (142 ± 23 vs 158 ± 26 mmHg, p = 0,001) but not at maximal exercise (189 ± 31 vs 201 ± 23 mmHg, p = NS), and, had lower actual maximal heart rate (155 ± 23 vs 143 ± 25 bpm, p = 0,03). There was no difference between obese patients with or without MS. ConclusionObese people with or without MS present with similar and normal aerobic profile related to the excessive body weight. VO2peak divided by weightBMI24 is an easy and clinical meaningful index for obese patients.

ALTERAÇÕES FISIOLÓGICAS E BIOQUÍMICAS NO PÓS-TREINO DE ALTA INTENSIDADE EM ADOLESCENTES

ABSTRACT Introduction Exercise intensity can approach an individual’s maximum capacity rapidly. High-intensity exercise can improve aerobic capacity in obesity, overweight, heart disease, and diabetes. Knowledge of the physiological and biochemical changes in the post-workout period could provide safety indexes for a scientific basis. Objective To evaluate the immediate physiological and biochemical changes in adolescents submitted to high-intensity sports training. Methods The article selects several young athletes for research. They were randomly divided into two groups. Group A did high-intensity exercise, and group B did regular exercise. A statistical analysis of physiological and biochemical indicators of athletes before and after exercise is done. Results The vital capacity in the two groups was significantly different. However, no significant differences were found between the biochemical indicators collected before and after training. Conclusion High-intensity sport can improve cardiopulmonary function with low impact on biochemical indicators. These findings indicate high-intensity physical training can improve sports performance without compromising the health of adolescents. Evidence Level II; Therapeutic Studies - Outcome Research.

Contribution of lung function in predicting distance covered in the 6-min walk test in obese Brazilian women.

Obesity affects the respiratory system through various mechanisms, including systemic inflammation and direct mechanical hindrance due to fat deposition in the chest and abdomen. In addition, changes in the neural control of respiration and increases in thoracic blood volume can promote abnormalities in lung function. Thus, determining relationships between the distance covered in the 6-min walk test (6MWT) and demographic and lung function variables may help us better understand the mechanisms involved in reduced functional exercise capacity in obesity. To explore the determinants of the 6-min walking distance (6MWD) and evaluate the influence of lung function on the distance covered, 263 obese Brazilian women performed the 6MWT and underwent spirometry and respiratory muscle strength measurement. The mean age was 41.8±11.1 years. The mean body mass index (BMI) was 45±8 kg/m2. The 6MWD showed correlations with height (r=0.319), age (r=-0.281), weight (r=-0.370), BMI (r=-0.561), forced vital capacity (FVC, r=0.443), expiratory peak flow (r=0.278), maximal inspiratory pressure (MIP, r=0.326), and maximal expiratory pressure (r=0.259), all with P<0.0001. In the stepwise forward regression analysis, BMI, FVC, age, and MIP were the independent predictive variables for 6MWD, explaining 41% of its variability. The reference equation including lung function was as follows: 6MWD (m) = 513.6 - (4.439 × BMIkg/m2) + (1.136 × FVC%predicted) - (1.048 × ageyrs) + (0.544 × MIP%predicted). Thus, the inclusion of lung function in a reference equation for 6MWD contributes to a better prediction of the distance covered in this population.

Adipose Mitochondrial Respiratory Capacity in Obesity is Impaired Independently of Glycemic Status of Tissue Donors.

The study aimed to investigate how obesity and glycemic state affect mitochondrial respiration and ATP-generating pathways in mature human adipocytes. Subcutaneous (sc) and visceral (vc) adipocytes were isolated from patients undergoing abdominal surgery. Respiratory chain function was analyzed by high-resolution respirometry. Adipocyte ATP levels and lactate release were measured separately in the presence of either glycolysis (2-deoxy-D-glucose) or ATP synthase (oligomycin) inhibitors. A significant negative correlation between oxidative phosphorylation capacity and the BMI of tissue donors found in sc adipocytes (P<0.05). Furthermore, respirometry revealed an inverse relationship between BMI and the electron transfer system capacity of sc (P<0.05) but not vc adipocytes. In both depots, the respiratory capacity was not affected by the glycemic state. A positive correlation between BMI and adipocyte lactate release was measured independently of the tissue origin (sc: P=0.01; vc: P<0.05). Direct ATP measurements indicated that energy demands of adipocytes were predominantly fulfilled by glycolytic activity. The study's data suggest that obesity is the primary driver of impaired adipocyte mitochondrial respiration because the glycemic state did not further deteriorate this situation. The adipocytes' energy needs are covered primarily by the glycolytic pathway.

Interaction between HFE and haptoglobin polymorphisms and its relation with plasma glutathione levels in obese children

Obesity among children has emerged as a serious public health problem. The growing prevalence of childhood obesity has led to the appearance of serious complications, including a chronic systemic inflammation associated with oxidative stress. In the present study, we analysed the interaction between two genes related with iron metabolism - HFE and haptoglobin - and the plasmatic concentration of glutathione, as a way to evaluate the antioxidant response capacity in obesity. To achieve this, 118 obese children and 89 eutrophic children were recruited for the study. Results showed that although obese children present a significantly decreased tGSH levels, once we analysed separately children based on their haptoglobin phenotype, the decreased tGSH levels is significant only for the Hp 2 allele. Additionally, Hp 2.2 obese children carrying H63D polymorphism show significantly lower tGSH/GSSG values. Our results found an association of haptoglobin and HFE with oxidative stress in childhood obesity.

Developing the capacity of general practice staff to support healthier weight status in children

BackgroundLambeth has implemented a healthy weight care pathway including capacity building of multi-agency staff. Successes include being the only borough in the country to see statistical reductions in childhood obesity over 5 years; but the challenge of 39.2% of 10–11-year olds leaving primary school as overweight/obese persists. When families approach GPs to validate the National Child Measurement Programme feedback, challenges include interpretation and explanation of body mass index (BMI). GPs have also felt uncomfortable raising the issue in routine consultations.AimTo understand potential enablers to raising the issue of unhealthy weight in children in general practice.Method70 staff (GPs 58%; Nurses 25%; GP registrar/trainee 7%; and HCA/other 10%) completed a bespoke childhood obesity capacity building workshop (accredited by the Royal College of GPs). Using scenario-based activities and end of session written questionnaire we gathered: knowledge and perceptions of weight measures, role of diet, nutrition and physical activity, as well as current blocks and potential enablers for brief intervention.ResultsLess than 5% of participants were able to identify a very overweight child by visual inspection. Confidence in raising the issue was reported due to enhanced knowledge of energy intake, physical activity and provision of a BMI wheel (40%), new ways of raising the issue (30%), understanding of supportive services in Lambeth (30%).ConclusionSupportive measures identified within a whole systems approach including role of schools, government, public health and the CCG are informing future planning.

Innate lymphoid cells as novel regulators of obesity and its-associated metabolic dysfunction.

The increased prevalence of obesity worldwide has been accompanied by increases in risk and rates of obesity-associated metabolic dysfunctions, such as insulin resistance. The chronic, low-grade inflammatory condition of obesity highlights the pathophysiological link between the immune system and the metabolic system, which has yet to be fully understood. Recent studies of obesity have started to uncover potential regulatory roles for the innate lymphoid cells (ILCs), which under normal conditions serve to regulate development of lymphoid tissue and function of the mucosal immune system. The ILCs are a newly identified immune cell population with complicated composition and subsequently diverse and dynamic functions. Studies to determine the distribution profile of the various ILCs in adipose tissue provide intriguing clues as to their regulatory capacity in obesity and its associated metabolic dysfunctions. Here, we review the recent findings supporting a role for ILCs as regulators of obesity or its associated insulin resistance, and discuss the potential underlying molecular mechanism as well as its promise as a therapeutic target for clinical applications. © 2016 World Obesity.

Altered executive function in obesity. Exploration of the role of affective states on cognitive abilities

There is a growing evidence that obesity is not only a weight problem, but it is linked to adverse neurocognitive outcomes. Besides obesity, frontal lobe based cognitive deficits in depressed patients are confirmed, and interactions between depression and obesity are known. In our study we investigated the relationship between cognitive functioning, mood and female obesity. Our findings revealed reduced mental flexibility and sustained attention capacity in obesity together with the presence of depressive mood. The mediating role of depression is confirmed. Positive emotion was associated with cognitive functions independently from BMI. Positive affectivity in obesity treatment is discussed.

Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content

In obesity and type 2 diabetes, exercise combined with weight loss increases skeletal muscle mitochondrial capacity. It remains unclear whether mitochondrial capacity increases because of weight loss, improvements in insulin resistance, or physical training. In this study, we examined the effects of an intervention of weight loss induced by diet and compared these with those of a similar intervention of weight loss by diet with exercise. Both are known to improve insulin resistance, and we tested the hypothesis that physical activity, rather than improved insulin resistance, is required to increase mitochondrial capacity of muscle. Sixteen sedentary overweight/obese volunteers were randomized to a 16-week intervention of diet (n = 7) or diet plus exercise (n = 9). Insulin sensitivity was measured using euglycemic clamps. Mitochondria were examined in muscle biopsies before and after intervention. We measured mitochondrial content and size by electron microscopy, electron transport chain (ETC) activity, cardiolipin content, and mitochondrial DNA content. Intramyocellular content of lipid (IMCL) and fiber-type distribution were determined by histology. The diet-only and diet plus exercise groups achieved similar weight loss (10.8 and 9.2%, respectively); only the diet plus exercise group improved aerobic capacity. Insulin sensitivity improved similarly in both groups. Mitochondrial content and ETC activity increased following the diet plus exercise intervention but remained unchanged following the diet-only intervention, and mitochondrial size decreased with weight loss despite improvement in insulin resistance. IMCL decreased in the diet-only but not in the diet plus exercise intervention. Despite similar effects to improve insulin resistance, these interventions had differential effects on mitochondria. Clinically significant weight loss in the absence of increased physical activity ameliorates insulin resistance and IMCL but does not increase muscle mitochondrial capacity in obesity.

Ventilatory response to exercise in simulated obesity by chest loading.

Obesity-related increases of weight on the chest wall are known to decrease lung volume and chest wall compliance, but the effect of this mass loading, independent of other obesity-related complications on the ventilatory response to exercise is unknown. The purpose of this study was to investigate the effect of chest mass loading on the ventilatory response to exercise. External chest loading (CL) was used to simulate the effect of moderate obesity (BMI = 32 kg x m). Eight healthy nonobese subjects performed two incremental exercise tests on a cycle ergometer with work rate increasing 25 W every 3 min once without (control; CON) and once with CL. Expiratory reserve volume (ERV), forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) were measured before each test. During exercise, inspiratory capacity (IC), to estimate changes in end-expiratory lung volume, and inspiratory (TI) and expiratory (TE) duration, tidal volume (Vt), breathing frequency (Fb), minute ventilation (VE), mean inspiratory (Vt/TI) and expiratory (Vt/TE) flow rates, and oxygen consumption (VO2) were measured. Baseline ERV, FVC and FEV1 were lower with CL (P < 0.05). Compared with CON, the peak work rate achieved during exercise with CL was lower and VO2, VE, Fb, Vt/TI, and Vt/TE were higher, and Vt was lower at work rates > or = 100 W (P < 0.05). IC increased progressively in CON during exercise but remained unchanged with CL. Obesity-related chest loading decreases lung volumes and increases the mechanical ventilatory constraints during exercise and is likely a critical factor in reducing exercise capacity in obesity.

A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice.

Endogenous lipid stores are thought to be involved in the mechanism whereby the beta-cell adapts its secretory capacity in obesity and diabetes. In addition, hormone-sensitive lipase (HSL) is expressed in beta-cells and may provide fatty acids necessary for the generation of coupling factors linking glucose metabolism to insulin release. We have recently created HSL-deficient mice that were used to directly assess the role of HSL in insulin secretion and action. HSL(-/-) mice were normoglycemic and normoinsulinemic under basal conditions, but showed an approximately 30% reduction of circulating free fatty acids (FFAs) with respect to control and heterozygous animals after an overnight fast. An intraperitoneal glucose tolerance test revealed that HSL-null mice were glucose-intolerant and displayed a lack of a rise in plasma insulin after a glucose challenge. Examination of plasma glucose during an insulin tolerance test suggested that HSL-null mice were insulin-resistant, because plasma glucose was barely lowered after the injection of insulin. Freshly isolated islets from HSL-deficient mice displayed elevated secretion at low (3 mmol/l) glucose, failed to release insulin in response to high (20 mmol/l) glucose, but had a normal secretion when challenged with elevated KCl. The phenotype of heterozygous mice with respect to the measured parameters in vitro was similar to that of wild type. Finally, the islet triglyceride content of HSL(-/-) mice was 2-2.5 fold that in HSL(-/+) and HSL(+/+) animals. The results demonstrate an important role of HSL and endogenous beta-cell lipolysis in the coupling mechanism of glucose-stimulated insulin secretion. The data also provide direct support for the concept that some lipid molecule(s), such as FFAs, fatty acyl-CoA or their derivatives, are implicated in beta-cell glucose signaling.