Normal-weight Control Subjects Research Articles

Abstract MP16: Degree of Joint Risk Factor Control and Incident Chronic Kidney Disease Among Obese Individuals

Introduction: Individuals who are obese are at a higher risk for chronic kidney disease (CKD) than the non-obese population. Hypothesis: We assessed the hypothesis that controlling joint risk factors might reduce the increased risk of CKD observed in participants with obesity. Methods: We included a total of 97,538 participants who were obese at baseline and matched 97,538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on 6 major CKD risk factors, including blood pressure, hemoglobin A1c, low-density lipoprotein cholesterol, albuminuria, smoking, and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD. Results: Among obese participants, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (HR: 0.89, 95%CI: 0.86-0.91) reduced risk of CKD among obese participants; with the optimal controlling of all six risk factors associated with a 49% (HR: 0.51, 95% CI: 0.43-0.61) decrease in risk of CKD. Furthermore, in obese individuals who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared to normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared to women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to nonusers ( P for interaction=0.017, 0.033, 0.014 respectively). Conclusion: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among obese people. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

The Association between Blood SIRT1 and Ghrelin, Leptin, and Antibody Anti-Hypothalamus: A Comparison in Normal Weight and Anorexia Nervosa.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, regulating metabolic homeostasis as well as leptin and ghrelin, and it could be considered as a potential plasmatic marker. The aim of this study was to assess whether circulating SIRT1 varies consistently with leptin, ghrelin, body mass index (BMI), and IgG reactive to hypothalamic antigens in anorexia nervosa (AN). Fifty-four subjects were evaluated: 32 with AN and 22 normal-weight control subjects. Serum levels of SIRT1, leptin, ghrelin, and IgG reactive to hypothalamic antigens were evaluated by ELISA. Results showed that serum SIRT1 is increased in patients with AN, and the amount is decreased in relation to the duration of the illness. SIRT1 concentration approaches the values obtained for the control group, although the difference is still statistically significant. A negative correlation between serum SIRT1 values and leptin or BMI values has been found. On the contrary, a positive correlation between SIRT1 and ghrelin or IgG specific for hypothalamic antigens is reported. These findings suggest that a peripheral evaluation of SIRT1 could be a possible clinical/biochemical parameter related to AN. In addition, we can assume that SIRT1 is related to autoantibody production and may correlate with the intensity/severity of AN. Thus, reducing the production of autoantibodies specific for hypothalamic cells could be a sign of improvement of the clinical condition.

Impacts of Adiposity on the Attentional Cost of Sensory-Motor Performance Associated with Mobility in a Dual-Task Paradigm.

(1) Background: Obesity is one of the most prevalent health problems worldwide. Studies have evidenced that the increase in body weight affects the normal neuromusculoskeletal function, which leads to abnormal gait patterns and impaired balance. (2) Objective: The aim of this study was to examine the influence of dual-task activity (cognitive-motor task) on gait parameters and balance among obese students. (3) Material and methods: A cross-sectional study was conducted among students (18–28 years old), including 120 obese and 120 age-matched normal-weight control subjects, selected at random using simple random sampling, from the Majmaah, Riyadh, Dammam, and Jizan regions of Saudi Arabia. The gait speed was measured in seconds while the controls and the obese subjects performed a dual-task activity of walking down a level, well-lit, narrow lane at their own speed, counting backwards from 100 by 4 s. (4) Results: The results of our study suggest a significant difference in the effect of the dual-task paradigm on the gait speed (t = 21.05, p = 000) of obese participants when compared to their age-matched counterparts. A significant correlation was found between BMI and gait speed and balance, irrespective of the gender of the obese student. A high degree of positive correlation (r = 0.705, p < 0.001) was found between BMI and gait speed, and a high degree of inverse correlation (r = −0.648, p < 0.001) was found between BMI and balance among obese students A multiple regression model explained 60% of the variance in gait speed and was statistically significant (R2 = 0.60, F (4, 235) = 90.65, p = 0.000) with BMI (β = 0.018, p = 0.000) and balance (β = 0.015, p = 0.000) significantly predicting gait speed. (5) Conclusion: The results of the current study provide evidence that obesity significantly influences gait speed and balance due to the inclusion of a contemporaneous cognitive task. The results also suggest that the dual-task paradigm affects both genders equally.

Effect of lipophilicity on drug distribution and elimination: Influence of obesity.

For a given passively-distributed lipophilic drug, the extent of in vivo distribution (pharmacokinetic volume of distribution, Vd ) in obese individuals increases in relation to the degree of obesity. The present study had the objective of evaluating drug distribution in relation to in vitro lipophilicity, and the relative increase in Vd associated with obesity across a series of drugs. Cohorts of normal-weight control and obese subjects received single doses of drugs ranging from hydrophilic (acetaminophen, salicylate) to lipophilic (imipramine, verapamil). Lipid solubility was measured by the log-transformed values of the high-pressure liquid chromatographic (HPLC) retention index (Log10 (HPLC)), and the octanol-water partition coefficient (LogP). Among normal-weight controls, Vd normalized for protein binding was highly correlated with Log10 (HPLC) (R2 = .65) and with LogP (R2 = .78). Vd of all drugs was increased in the obese cohort, but the relative increase (compared to controls) for individual drugs was disproportionately greater as lipid solubility increased. Since clearance was unrelated to lipophilicity, the increased Vd produced a parallel disproportionate increase in elimination half-life in the obese cohort that was associated with Log10 (HPLC) (R2 = .62). Lipophilicity is a principal correlate of in vivo Vd , as well as the increased Vd of drugs in obese patients. The consequent prolongation of half-life in obesity has clinical safety implications in terms of delayed drug accumulation and washout during and after chronic dosage. The magnitude and importance of this effect for a given drug depends on the degree of obesity, as well as the lipid-solubility of the specific drug.

Distribution and effect of ghrelin genotype on plasma lipid and apolipoprotein profiles in obese and nonobese Chinese subjects.

The hormone ghrelin has an important role in a wide range of metabolic and nonmetabolic processes. Ghrelin gene polymorphisms have been reported to influence obesity or lipid abnormalities in some ethnic groups. This study was conducted mainly to examine the possible association of ghrelin - 604G > A and Leu72Met polymorphisms with obesity and related traits in a Southwest Chinese population. Three hundred and eighty-six Han Chinese individuals (118 obese and 268 normal weight control subjects) in the Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Clinical and biochemical parameters were also analyzed. The genotype and allele frequencies of ghrelin gene polymorphisms in participants with obesity showed no significant difference compared to those in nonobese controls. However, in the nonobese control group, carriers of genotype Met/Met at the Leu72Met site had higher serum TC and LDL-C concentrations than those of the Leu/Leu genotype (P < 0.05). When nonobese subjects were stratified by sex, the genotype-dependent effects on TC and LDL-C were more evident, although this was observed only in females. In addition, genotype-related effects on these lipid parameters at this site were observed in male obese subjects only. The Leu72Met polymorphism of the ghrelin gene is associated with altered plasma TC and LDL-C concentrations, and the effects on TC and LDL-C levels are sex-dependent in both nonobese and obese subjects in the Chinese population of the Chengdu area.

Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile.

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (-17%, p < 0.01) and type IIA (-14%, p < 0.05) muscle fibers, a lower glycogen content for type I (-6%, p < 0.01) and type IIA (-5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (-20%, p < 0.001), a low capillary-to-fiber ratio (-19%, p < 0.001), and low citrate synthase activity (-18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

Pubertal Lipid Levels Are Significantly Lower in Youth With Type 1 Diabetes Who Experienced Partial Clinical Remission.

ImportanceThe physiologic changes in lipids during puberty in type 1 diabetes (T1D) are unclear because subjects in previous studies were not stratified by partial clinical remission status.AimTo determine the effect of partial clinical remission on lipid changes during puberty in youth with T1D.Subjects and MethodsA retrospective cross-sectional study of 194 subjects consisting of 71 control subjects of age 12.9 ± 1.3 years and 123 subjects with T1D stratified into remitters (n = 44; age, 13.0 ± 0.8 years) and nonremitters (n = 79; age, 11.2 ± 0.6 years). Partial clinical remission was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging.ResultsAmong the pubertal cohort, low-density lipoprotein cholesterol concentration was significantly higher in the nonremitters compared with remitters (91.1 ± 25.6 vs 77.2 ± 25.8 mg/dL, P = 0.018) and with normal-weight control subjects (91.1 ± 25.6 vs 70.4 ± 22.9 mg/dL, P = 0.009) but was similar between overweight/obese control subjects and nonremitters (89.7 ± 28.9 vs 91.1± 25.6 mg/dL, P = 0.81) and between normal-weight control subjects and remitters (70.4 ± 22.9 vs 77.2 ± 25.8 mg/dL, P = 0.39). Total cholesterol was also significantly higher in nonremitters compared with remitters (167.8 ± 30.5 vs 149.8 ± 32.1 mg/dL, P = 0.012) and with normal-weight control subjects (167.8 ± 30.5 vs 143.2 ± 30.1 mg/dL, P = 0.011) but was similar between nonremitters and overweight/obese control subjects (P = 0.098) and between remitters and normal-weight control subjects (P = 0.51). Non–high-density lipoprotein cholesterol was equally significantly higher in nonremitters compared with remitters (111.3 ± 30.1 vs 95.9 ± 29.1 mg/dL, P = 0.028) and normal-weight control subjects (111.3 ± 30.1 vs 86.2 ± 32.2 mg/dL, P = 0.028) but was similar between nonremitters and overweight/obese control subjects (P = 0.48) and between remitters vs normal-weight control subjects (P = 0.39).ConclusionsPuberty-related reductions in low-density lipoprotein, total cholesterol, and non–high-density lipoprotein occur in remitters and normal-weight control subjects but not in nonremitters and overweight/obese control subjects.

Feasibility Evaluation of Myocardial Cannabinoid Type 1 Receptor Imaging in Obesity: A Translational Approach

ObjectivesThe aim of this study was to evaluate the feasibility of targeted imaging of myocardial cannabinoid type 1 receptor (CB1-R) and its potential up-regulation in obese mice with translation to humans using [11C]-OMAR and positron emission tomography (PET)/computed tomography (CT). BackgroundActivation of myocardial CB1-R by endocannabinoids has been implicated in cardiac dysfunction in diabetic mice. Obesity may lead to an up-regulation of myocardial CB1-R, potentially providing a mechanistic link between obesity and the initiation and/or progression of cardiomyopathy. MethodsBinding specificity of [11C]-OMAR to CB1-R was investigated by blocking studies with rimonabant in mice. The heart was harvested from each mouse, and its radioactivity was determined by γ-counter. Furthermore, [11C]-OMAR dynamic micro-PET/CT was carried out in obese and normal-weight mice. Ex vivo validation was performed by droplet digital polymerase chain reaction (absolute quantification) and RNAscope Technology (an in situ ribonucleic acid analysis platform). Subsequently, myocardial CB1-R expression was probed noninvasively with intravenous injection of CB1-R ligand [11C]-OMAR and PET/CT in humans with advanced obesity and normal-weight human control subjects, respectively. ResultsRimonabant significantly blocked OMAR uptake in the heart muscle compared with vehicle, signifying specific binding of OMAR to the CB1-R in the myocardium. The myocardial OMAR retention quantified by micro-PET/CT in mice was significantly higher in obese compared with normal-weight mice. Absolute quantification of CB1-R gene expression with droplet digital polymerase chain reaction and in situ hybridization confirmed CB1-R up-regulation in all major myocardial cell types (e.g., cardiomyocytes, endothelium, vascular smooth muscle cells, and fibroblasts) of obese mice. Obese mice also had elevated myocardial levels of endocannabinoids anandamide and 2-arachidonoylglycerol compared with lean mice. Translation to humans revealed higher myocardial OMAR retention in advanced obesity compared with normal-weight subjects. ConclusionsNoninvasive imaging of cardiac CB1-R expression in obesity is feasible applying [11C]-OMAR and PET/CT. These results may provide a rationale for further clinical testing of CB1-R-targeted molecular imaging in cardiometabolic diseases.

Visceral obesity in the normal-weight people-comparing chronic schizophrenia and healthy control subjects

Visceral obesity in the normal-weight people-comparing chronic schizophrenia and healthy control subjects

Impact of body weight on the achievement of minimal disease activity in patients with rheumatic diseases: a systematic review and meta-analysis.

BackgroundIn this study, we evaluated the impact of obesity and/or overweight on the achievement of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) receiving an anti-rheumatic treatment. Obesity can be considered a low-grade, chronic systemic inflammatory disease and some studies suggested that obese patients with rheumatic diseases exhibit a lower rate of low disease activity achievement during treatment with anti-rheumatic drugs.MethodsA systematic search was performed in major electronic databases (PubMed, Web of Science, Scopus, Embase) to identify studies reporting MDA achievement in obese and/or overweight patients with RA or PsA and in normal-weight RA or PsA control subjects. Results were expressed as Odds Ratios (ORs) with pertinent 95% Confidence Intervals (95%CIs).ResultsWe included 17 studies (10 on RA and 7 on PsA) comprising a total of 6693 patients (1562 with PsA and 5131 with RA) in the analysis. The MDA achievement rate was significantly lower in obese patients than in normal-weight subjects (OR 0.447, 95% CI 0.346–0.577, p < 0.001, I 2 = 62.6%, p < 0.001). Similarly, overweight patients showed a significantly lower prevalence of MDA achievement than normal-weight subjects (OR 0.867, 95% CI 0.757–0.994, p = 0.041, I 2 = 64%, p = 0.007). Interestingly, the effect of obesity on MDA was confirmed when we separately analyzed data on patients with RA and patients with PsA. In contrast, when we evaluated the effect of overweight, our results were confirmed for PsA but not for RA. A meta-regression analysis showed that follow-up duration, age, male sex, and treatment duration are covariates significantly affecting the effect of obesity/overweight on MDA achievement.ConclusionsThe results of our meta-analysis suggest that obesity and overweight reduce the chances to achieve MDA in patients with rheumatic diseases receiving treatment with traditional or biologic disease-modifying antirheumatic drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1194-8) contains supplementary material, which is available to authorized users.

Anorexia Nervosa: Analysis of Trabecular Texture with CT.

Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group). All participants underwent low-dose single-section quantitative CT of the L4 vertebral body with use of a calibration phantom. Trabecular texture analysis was performed by using software. Skewness (asymmetry of gray-level pixel distribution), kurtosis (pointiness of pixel distribution), entropy (inhomogeneity of pixel distribution), and mean value of positive pixels (MPP) were assessed. Bone mineral density and abdominal fat and paraspinal muscle areas were quantified with quantitative CT. Women with anorexia nervosa and normal-weight control subjects were compared by using the Student t test. Linear regression analyses were performed to determine associations between trabecular texture and body composition. Results Women with anorexia nervosa had higher skewness and kurtosis, lower MPP (P < .001), and a trend toward lower entropy (P = .07) compared with control subjects. Bone mineral density, abdominal fat area, and paraspinal muscle area were inversely associated with skewness and kurtosis and positively associated with MPP and entropy. Texture parameters, but not bone mineral density, were associated with lowest lifetime weight and duration of amenorrhea in anorexia nervosa. Conclusion Patients with anorexia nervosa had increased skewness and kurtosis and decreased entropy and MPP compared with normal-weight control subjects. These parameters were associated with lowest lifetime weight and duration of amenorrhea, but there were no such associations with bone mineral density. These findings suggest that trabecular texture analysis might contribute information about bone health in anorexia nervosa that is independent of that provided with bone mineral density. © RSNA, 2016.

Cardiometabolic Health in Adults Born Premature With Extremely Low Birth Weight.

Young adults born with extreme prematurity have increased blood pressure and insulin resistance. This study documents their metabolic health as they enter their fourth decade of life. The study objective was to compare body composition, glycemia, lipid levels, and blood pressure in adults born with extremely low birth weight (ELBW) versus age- and sex- matched normal birth weight (NBW) control subjects and to examine related previous and current exposures. The study examines one of the oldest regionally representative cohorts of ELBW subjects (birth weight <1 kg) and NBW individuals born between 1977 and 1982. The primary outcome was dysglycemia (type 2 diabetes or prediabetes) based on results of a 75-g oral glucose tolerance test. Secondary outcomes include body composition, insulin resistance, fasting lipid profile, and blood pressure. Potential predictive factors included birth weight, maternal antenatal corticosteroid exposure, retinopathy of prematurity, growth parameters, and smoking history. Adults (mean age, 31.8 years) born ELBW (n = 100) had a higher percent body fat (P = .004) and lower lean mass for height (P = .018) but similar waist circumference (P = .54) and BMI (P = .61) compared with NBW control subjects. ELBW adults had a 4.0-fold (95% confidence interval, 1.53-10.66) increased risk of developing dysglycemia. Adults born ELBW also had higher systolic (P = .004) and diastolic (P = .02) blood pressures compared with NBW control subjects, but there were no differences in lipid profile. By their fourth decade, these adults born extremely premature had increased body fat, lower lean mass, and a 4-fold increased risk of developing dysglycemia.

Ectopic and Visceral Fat Deposition in Lean and Obese Patients With Type 2 Diabetes

BackgroundType 2 diabetes (T2D) and obesity are associated with nonalcoholic fatty liver disease, cardiomyopathy, and cardiovascular mortality. Both show stronger links between ectopic and visceral fat deposition, and an increased cardiometabolic risk compared with subcutaneous fat. ObjectivesThis study investigated whether lean patients (Ln) with T2D exhibit increased ectopic and visceral fat deposition and whether these are linked to cardiac and hepatic changes. MethodsTwenty-seven obese patients (Ob) with T2D, 15 Ln-T2D, and 12 normal-weight control subjects were studied. Subjects underwent cardiac computed tomography, cardiac magnetic resonance imaging (MRI), proton and phosphorus MR spectroscopy, and multiparametric liver MR, including hepatic proton MRS, T1- and T2*-mapping yielding “iron-corrected T1” [cT1]. ResultsDiabetes, with or without obesity, was associated with increased myocardial triglyceride content (p = 0.01), increased hepatic triglyceride content (p = 0.04), and impaired myocardial energetics (p = 0.04). Although cardiac structural changes, steatosis, and energetics were similar between the T2D groups, epicardial fat (p = 0.04), hepatic triglyceride (p = 0.01), and insulin resistance (p = 0.03) were higher in Ob-T2D. Epicardial fat, hepatic triglyceride, and insulin resistance correlated negatively with systolic strain and diastolic strain rates, which were only significantly impaired in Ob-T2D (p < 0.001 and p = 0.006, respectively). Fibroinflammatory liver disease (elevated cT1) was only evident in Ob-T2D patients. cT1 correlated with hepatic and epicardial fat (p < 0.001 and p = 0.01, respectively). ConclusionsIrrespective of body mass index, diabetes is related to significant abnormalities in cardiac structure, energetics, and cardiac and hepatic steatosis. Obese patients with T2D show a greater propensity for ectopic and visceral fat deposition.

Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner

Obesity is associated with multiple diseases. Bariatric surgery is the most effective therapy for severe obesity that can reduce body weight and obesity-associated morbidity. The metabolic alterations associated with obesity and respective changes after bariatric surgery are incompletely understood. We comprehensively assessed metabolic alterations associated with severe obesity and distinct bariatric procedures. In our longitudinal observational study, we applied a (1)H-nuclear magnetic resonance-based global, untargeted metabolomics strategy on human serum samples that were collected before and repeatedly ≤1 y after distinct bariatric procedures [i.e., a sleeve gastrectomy, proximal Roux-en Y gastric bypass (RYGB), and distal RYGB]. For comparison, we also analyzed serum samples from normal-weight and less-obese subjects who were matched for 1-y postoperative body mass index (BMI) values of the surgical groups. We identified a metabolomic fingerprint in obese subjects that was clearly discriminated from that of normal-weight subjects. Furthermore, we showed that bariatric surgery (sleeve gastrectomy and proximal and distal RYGB) dynamically affected this fingerprint in a procedure-dependent manner, thereby establishing new fingerprints that could be discriminated from those of BMI-matched and normal-weight control subjects. Metabolites that largely contributed to the metabolomic fingerprints of severe obesity were aromatic and branched-chain amino acids (elevated), metabolites related to energy metabolism (pyruvate and citrate; elevated), and metabolites suggested to be derived from gut microbiota (formate, methanol, and isopropanol; all elevated). Our data indicate that bariatric surgery, irrespective of the specific kind of procedure used, reverses most of the metabolic alterations associated with obesity and suggest profound changes in gut microbiome-host interactions after the surgery. This trial was registered at clinicaltrials.gov as NCT02480322.

Biological and Social Influences on Outcomes of Extreme-Preterm/Low-Birth Weight Adolescents.

The importance of biological versus social influences on long-term outcomes of extremely preterm children is debatable. The goal of this study was to determine the relative contributions of biological and social exposures to outcomes into adolescence in extremely preterm survivors, hypothesizing that biological exposures would be more important early, but social exposures would dominate later. The study included 298 consecutive survivors born at <28 weeks' gestation or weighing <1000 g in Victoria, Australia (during 1991-1992), and 262 normal birth weight (>2499 g) control subjects who were used to standardize outcomes for the preterm group. Cognitive ability was assessed at 2, 5, 8, and 18 years of age. Academic achievement was assessed at 8 and 18 years of age. The differences between the preterm and control groups for cognitive and academic scores remained relatively constant over time. The biological variables most associated with worse outcomes within the extremely preterm group were intraventricular hemorrhage and postnatal corticosteroid therapy. Of the social variables, being reared in a multilingual household was disadvantageous early, with social class and maternal education becoming more important for later outcomes. The strength of the biological associations mostly equaled or exceeded those of social exposures, even in late adolescence. Contrary to expectations, several perinatal biological exposures had large and persistent adverse associations with cognitive and academic outcomes among extremely preterm survivors. As expected, some social variables assumed increasing importance in later years but mostly did not diminish or exceed the important biological associations.

Differential effects of GLP-1 receptor agonist on foam cell formation in monocytes between non-obese and obese subjects

ObjectiveMonocytes/macrophages (Mϕ) transform into foam cells in the presence of oxidized-LDL (ox-LDL), releasing inflammatory mediators. The antiatherogenic role of a dipeptidyl peptidase-4 inhibitor is mediated, in part, through improving the unbalance of inflammatory (M1)/anti-inflammatory (M2) phenotypes in monocytes. In this study, we examined differential regulation of glucagon-like peptide-1 receptor (GLP-1R) signaling for antiatherogenesis in monocytes/Mϕ from normal-weight control subjects and obese patients. MethodsWe evaluated the effects of exendin-4 (Ex-4), a GLP-1R agonist, on ox-LDL-stimulated foam cell formation, M1/M2 cytokine production, and organelle change in primary monocytes from control subjects and obese patients and human monocytic THP-1-derived Mϕ as well. ResultsHere we report that Ex-4 suppressed foam cell formation and M1 cytokine expression and, interestingly, induced indicators of autophagy in ox-LDL-stimulated monocytes from control subjects. The suppressing effects on foam cell formation by Ex-4 were reversed by a cAMP inhibitor. In contrast to control subjects, Ex-4 did not induce indicators of autophagy, but did induce foam cell formation and M1 cytokine expression in monocytes from obese patients. GLP-1R expression level was comparable between control subjects and obese patients. The effects of Ex-4 on inducing indicators of autophagy and suppressing foam cell formation were observed in THP-1 Mϕ. ConclusionsThese data suggest that GLP-1R signaling induces autophagy, thereby suppressing foam cell formation in non-obese subjects. In obese patients, GLP-1R stimulation increased foam cell formation and IL-6, TNF-α, and IL-1β production. Such altered signaling in monocytes of obese patients may be involved in the development of atherosclerosis.

Enhanced neural responsiveness to reward associated with obesity in the absence of food-related stimuli.

Obesity has been characterized by alterations in brain structure and function associated with emotion processing and regulation. Particularly, aberrations in food-related reward processing have been frequently demonstrated in obese subjects. However, it remains unclear whether reward-associated functional aberrations in obesity are specific for food-related stimuli or represent a general deficit in reward processing, extending to other stimulus domains. Given the crucial role of rewarding effects in the development of obesity and the ongoing discussion on overlapping neurobiological traits of obesity and psychiatric disorders such as depression and substance-related disorders, this study aimed to investigate the possibility of altered reward processing in obese subjects to occur in the absence of food-related stimuli during a monetary reward condition. Twenty-nine healthy obese subjects (body mass index >30) and 29 healthy, age-, and sex-matched control subjects of normal weight underwent functional MRI during a frequently used card guessing paradigm. A Group × Condition (win vs. loss) ANOVA was conducted to investigate differences between obese and normal-weight subjects. We found significant Group × Condition interaction effects in brain areas involved in emotion regulation and reward processing including the insula, the striatum, and the orbitofrontal cortex (OFC). This interaction was predominantly driven by a significant increase in blood oxygenation level dependent (BOLD) response in obese individuals while experiencing reward. Enhanced neural activation in obesity during reward processing seems to be apparent even in the absence of food-related stimuli and, thus, might point to generalized dysfunctions in reward-related brain circuits in obese individuals.

Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention.

Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12‐week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real‐time PCR of mRNA of lipid droplet‐associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large‐scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training.

Enhanced upper-airway muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea.

Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m(2)) for reasons that are not fully elucidated. To determine the key physiologic traits (upper-airway anatomy/collapsibility, upper-airway muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals. We compared key physiologic traits in 18 overweight/obese subjects without apnea (apnea-hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea-hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep. Overweight/obese subjects without apnea exhibited a less collapsible airway than overweight/obese patients with apnea (critical closing pressure: -3.7 ± 1.9 vs. 0.6 ± 1.2 cm H2O; P = 0.003; mean ± 95% confidence interval), but a more collapsible airway relative to normal-weight control subjects (-8.8 ± 3.1 cm H2O; P < 0.001). Notably, overweight/obese subjects without apnea exhibited a threefold greater upper-airway muscle responsiveness than both overweight/obese patients with apnea (Δgenioglossus EMG/Δepiglottic pressure: -0.49 [-0.22 to -0.79] vs. -0.15 [-0.09 to -0.22] %max/cm H2O; P = 0.008; mean [95% confidence interval]) and normal-weight control subjects (-0.16 [-0.04 to -0.30] %max/cm H2O; P = 0.02). Loop gain was elevated (more negative) in both overweight/obese groups and normal-weight control subjects (P = 0.02). Model-based analysis demonstrated that overweight/obese individuals without apnea rely on both more favorable anatomy and collapsibility and enhanced upper-airway dilator muscle responses to avoid OSA. Overweight/obese individuals without apnea have a moderately compromised upper-airway structure that is mitigated by highly responsive upper-airway dilator muscles to avoid OSA. Elucidating the mechanisms underlying enhanced muscle responses in this population may provide clues for novel OSA interventions.

Plasma nesfatin-1 level in obese patients after acupuncture: a randomised controlled trial.

Nesfatin-1 is an anorexigenic hormone suggested to regulate obesity. To investigate the relationship between nesfatin-1 level and anthropometric and metabolic parameters in obese patients, and examine the change in plasma nesfatin-1 level after acupuncture treatment. 64 obese adult patients without diabetes and 58 normal weight control subjects were enrolled in this study. The obese patients were randomly divided into an acupuncture plus diet group (n=32) and a diet only group (n=32). Measurements were repeated after 45 days. Body mass index (BMI), waist and hip circumferences, serum insulin, lipoprotein and insulin resistance measures were significantly higher, and plasma nesfatin-1 level was significantly lower, in obese patients than in normal weight controls. In addition, negative correlations were found between plasma nesfatin-1 level and BMI, waist and hip circumferences. Weight reduction in participants after acupuncture and diet restriction was 7.0% and 4.3%, respectively. Plasma nesfatin-1 level increased from 2.75±1.16 to 3.44±1.28 ng/mL and from 2.86±1.07 to 3.23±1.06 ng/mL in acupuncture and diet groups, respectively; the difference was significant, p<0.05. Plasma nesfatin-1 level is reduced in obese adults, and is increased after acupuncture. The beneficial effect of acupuncture on obesity is associated with increased plasma nesfatin-1 level.