Nonobese Control Subjects Research Articles

PP239-MON IS THERE A POSITIVE INFLUENCE OF THE AMINOACID COMPOUND CONTAINING ARGININE, β-HYDROXY-β-METHYLBUTYRATE AND GLUTAMINE ON WOUND HEALING?

Body Mass index for RYBP patients before surgery was 47.3±8.2 kg/m2, and after surgery 31.3±5 kg/m2. All patients had a % of excessive body weight loss >50%. RYGBP patients and non-obese healthy control subjects had significantly different citrulline (25.5±4.3 vs. 33.0±7.5 umol/L respectively; p < 0.01) and arginine (56.0±12.2 vs. 71.2±14.9mg/dL; p < 0.05) plasma levels. Participants had normal creatinine values (0.7 1.4mg/dL for men and 0.6 1.2mg/dL for women). Conclusion: Following Roux-en-y gastric bypass, the decrease in enterocyte mass is illustrated by a citrullinemia lower than normal, which in turn likely explains hypoargininemia. The clinical significance (e.g. in term of immune and healing functions) of the latter should be explored as well as the interest of supplementation.

Adipogenic differentiation of adipose tissue-derived human mesenchymal stem cells: effect of gastric bypass surgery

Adipose tissue dysfunction is an important feature of obesity characterized by enlarged adipocytes and marked changes in secretion of cytokines. These changes result in insulin resistance, chronic vascular inflammation, oxidative stress, and activation of the renin-angiotensin system (RAS), eventually leading to type 2 diabetes, obesity-related hypertension, and cardiovascular disease (CVD). Several trials have shown that bariatric surgery significantly reduces these comorbidities. However, there is a gap in knowledge regarding the mechanisms whereby bariatric surgery reduces the burden of CVD in obese individuals. Mesenchymal stem cells (MSCs) were isolated from adipose tissue collected from three groups: (1) nonobese control subjects, (2) obese subjects undergoing gastric bypass surgery (GBS), and (3) subjects 1year or more after GBS. In the study, MSCs were induced to adipogenic differentiation, and RAS-related gene expressions were determined by quantitative polymerase chain reaction. The effect of angiotensin II (Ang II) on adipogenic differentiation of MSCs also was investigated. Angiotensinogen mRNA levels in MSCs and differentiated adipocytes were significantly higher in the obese group than in the nonobese control subjects. Renin mRNA levels were significantly higher in the obese group MSCs than in the nonobese and post-GBS groups. Angiotensin-converting enzyme mRNA levels were significantly lower in the MSCs derived from the post-GBS group than in the obese and nonobese control subjects. Serum Ang II levels were significantly lower in the post-GBS group (52.1±4.2pg/ml) than in the nonobese (85.4±12.4pg/ml) and obese (84.7±10.0pg/ml) groups. Ang II treatment inhibited adipogenesis of MSCs in a dose-dependent manner. The inhibitory effect of Ang II was mainly abolished by PD123319, a receptor 2 blocker. The adipogenesis of MSCs is inhibited by Ang II treatment. Obese individuals are characterized by an upregulation of the RAS-related gene expressions in adipose tissue. This upregulation resolves in post-GBS subjects.

Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk

Oxidative and inflammatory stresses are involved in the pathogenesis of atherosclerosis. The consumption of fruit and vegetables is associated with improved health and reduced cardiovascular risk. Red oranges have a high content of antioxidant and antiinflammatory substances, but there is a paucity of data concerning their effects on cardiovascular biomarkers in subjects with increased cardiovascular risk. We investigated the effect of red orange juice intake on endothelial function, oxidative stress, and markers of inflammation in subjects with increased cardiovascular risk. Nineteen nondiabetic subjects with increased cardiovascular risk (aged 27-56 y) were included in a randomized, placebo-controlled, single-blind crossover study and compared with 12 healthy, nonobese control subjects. In 2 periods of 7 d each with a 3-d interval, each participant alternatively received 500 mL red orange juice/d and 500 mL placebo/d in a random sequence. All measurements were performed in the morning after overnight fasting. Endothelial function, which was measured as flow-mediated dilation, significantly improved and was normalized (5.7% compared with 7.9%; P < 0.005) after 1 wk of red orange juice consumption. Similarly, concentrations of high-sensitivity C-reactive protein, IL-6, and TNF-α significantly decreased (P < 0.001). Red orange juice had no significant effect on nitric oxide plasma concentrations. A 7-d consumption of red orange juice ameliorates endothelial function and reduces inflammation in nondiabetic subjects with increased cardiovascular risk. This trial was registered at biomedcentral.com as ISRCTN39987296.

Association Study ofApolipoprotein L-ILys166Glu and Ile244Met Gene Variants with Obesity in Chinese Subjects

ApoL-I is a newly found component of high-density lipoprotein, and has a potential role in lipid metabolism. This study was mainly to examine the possible association of the ApoL-I gene polymorphism with obesity and plasma lipid levels in the Chinese population. Three hundred nineteen Han Chinese (109 obese and 210 nonobese control subjects) in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphism analysis. The Lys and Glu allele frequencies of the apoL-I gene at the Lys166Glu site in obese and nonobese control groups were 0.830, 0.170 and 0.814, 0.186, respectively. The Ile and Met allele frequencies of the gene at Ile244Met site in the obese and the control groups were 0.844, 0.156 and 0.831, 0.169, respectively. The 166Glu and 244Met allele frequencies of the two polymorphisms in obese subjects were not different from those in the controls, respectively (p>0.05). In the nonobese group, subjects with genotype Lys/Lys at the Lys166Glu site or Ile/Ile at the Ile244Met site had a higher serum mean concentration of triglyceride (TG) as compared with those of corresponding Glu or Met allele carriers (p<0.05). In addition, serum apoC-III and apoE levels were affected by genotypes of Lys166Glu and Ile224Met polymorphisms, respectively, in the control group (all p<0.05). The current study, for the first time, provides evidence that Lys166Glu and Ile244Met polymorphisms in apoL-I gene are associated with TG, apoC-III, and apoE levels in nonobese Chinese. However, these polymorphisms are not associated with obesity in the population.

Non-Alcoholic Fatty Liver Disease and the Left Ventricle Mass Index in Obese Children

Objective: To investigate Nonalcoholic Fatty Liver Disease (NAFLD), the Left Ventricle Mass Index (LVMI), and the relationship between NAFLD and LVMI in obese children. Material and methods: Systolic (SBP) and Diastolic (DBP) Blood Pressure and waist and hip circumferences were measured. Fasting blood glucose and insulin concentrations, total cholesterol, and Triglycerides (TG) were assayed. The diagnosis of NAFLD was based on sonographic evidence of a fatty liver. The Left Ventricle Mass (LVM) was calculated from two-dimensionally guided M-mode echocardiographic measurements of the left ventricle. LVMI was calculated as LVM (g)/height (m)2.7 and Left Ventricular Hypertrophy (LVH) was defined as LVMI ≥ 95th percentile for age and gender Results: Forty-three obese children with NAFLD, 55 obese children without NAFLD, and 48 non-obese controls were studied. Fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, TG, and total cholesterol levels in the obese children were significantly higher than in the controls (all p 0.05). The prevalence of LVH differed significantly between the obese groups and controls (all p 0.05). In a multiple linear regression analysis, NAFLD, SBP, and DBP were not correlated with LVMI. The LVMI was closely related to the Body Mass Index-Standard Deviation Score (BMI-SDS), and Liver Longitudinal Dimension (LLD) percentile. The BMI-SDS was the only independent predictor of NAFLD and LVMI. Conclusions: LVH and NAFLD are two important and independent covariates in obese children. Obese children with or without hypertension have significant LVH as compared with non-obese control subjects. NAFLD and casual blood pressure measurements are not predictors of LVMI in obese children.

Association between adipocytokines and insulin resistance in Indian hypertensive patients

ObjectiveAlthough the relationship between obesity, hypertension (HT), and insulin resistance is well-recognised, the pathophysiological mechanism involved is relatively poorly understood. The present study aims in examining the relationship between adipocytokines and insulin resistance in Indian hypertensive patients to better understand the pathogenesis of HT. MethodsA total of 124 subjects including 41 controls, 41 obese, and 42 hypertensive patients were recruited in this cross-sectional study. Fasting adipocytokines (leptin, adiponectin, resistin) and highly sensitive C-reactive protein (hsCRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Insulin resistance (IR) index was calculated by the homeostasis model assessment (HOMA). The relation between these variables was studied by univariate and multiple logistic regression analysis. ResultsAmong the hypertensive patients, obese hypertensive patients exhibited significantly increased HOMA-IR and altered adipocytokine profile compared to the non-obese control subjects. In a stepwise multiple linear regression analysis with IR as a dependant variable, the study shows leptin as a significant predictor in hypertensive patients. Multiple logistic regression analysis revealed that among the adipocytokines, leptin had a strong association with HT in our population. ConclusionAmong the adipocytokine, serum leptin levels were significantly increased in hypertensive patients and were also associated with IR and HT. Thus, our findings suggest that leptin may be playing an important role in the development of HT in our population.

Serum leptin levels are inversely correlated with omental gene expression of adiponectin and markedly decreased after gastric bypass surgery

Adipose tissue is the most abundant endocrine tissue in the body, producing leptin, a hormone important in regulating hunger, and adiponectin, a hormone involved in insulin sensitivity and inflammation. This study aimed to assess the impact of gastric bypass surgery (GBS) on leptin levels and its relation to the adipose tissue expression of adiponectin. Omental and subcutaneous adipose tissue and serum were obtained from 40 obese patients undergoing GBS, from 13 patients 1 year or more after GBS, and from 16 non-obese individuals with a body mass index of 20 to 29 kg/m(2). Adiponectin gene expression was measured by quantitative real-time polymerase chain reaction, and the gene expression was normalized for the GAPDH gene. Serum leptin and adiponectin were measured by a high-sensitivity enzymatic assay. Leptin levels were significantly lower in the post-GBS patients (19.8 ± 6.7) than in the pre-GBS patients (59.0 ± 5.1; P = 0.0001), and similar to those in the non-obese control subjects (18.2 ± 4; P = 0.8). Univariate analysis showed an inverse correlation between serum leptin levels and omental adiponectin gene expression (r = -0.32; P = 0.01). Gastric bypass surgery results in resolution of the leptin resistance status that characterizes obese subjects. The study also demonstrated a significant correlation between leptin and adiponectin. This correlation provides preliminary evidence for studying a potential adiponectin-leptin cross-talking that may represent one of the physiologic pathways responsible for the regulation of food intake in humans.

Elevated NF-κB Activation Is Conserved in Human Myocytes Cultured From Obese Type 2 Diabetic Patients and Attenuated by AMP-Activated Protein Kinase

OBJECTIVETo examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes.RESEARCH DESIGN AND METHODSMuscle precursor cells were isolated from four age-matched subject groups: 1) nonobese, normal glucose tolerant; 2) obese, normal glucose tolerant; 3) obese, impaired glucose tolerant; and 4) obese, type 2 diabetes (T2D). The level of inflammation (nuclear factor-κB [NF-κB] signaling) and effect of pharmacological AMPK activation was assessed by Western blots, enzyme-linked immunosorbent assay, and radioactive assays (n = 5 for each subject group).RESULTSNF-κB-p65 DNA binding activity was significantly elevated in myocytes from obese T2D patients compared with nonobese control subjects. This correlated to a significant increase in tumor necrosis factor-α concentration in cell culture media. In addition, insulin-stimulated glucose uptake was completely suppressed in myocytes from obese impaired glucose tolerant and T2D subjects. It is interesting that activation of AMPK by A769662 attenuated NF-κB-p65 DNA binding activity in obese T2D cells to levels measured in nonobese myocytes; however, this had no effect on insulin sensitivity of the cells.CONCLUSIONSThis work provides solid evidence that differentiated human muscle precursor cells maintain in vivo phenotypes of inflammation and insulin resistance and that obesity alone may not be sufficient to establish inflammation in these cells. It is important that we demonstrate an anti-inflammatory role for AMPK in these human cells. Despite attenuation of NF-κB activity by AMPK, insulin resistance in obese T2D cells remained, suggesting factors in addition to inflammation may contribute to the insulin resistance phenotype in muscle cells.

The influence of obesity and obstructive sleep apnea on metabolic hormones

Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by excessive daytime sleepiness and repetitive upper airway obstruction episodes during sleep. Clinically, obesity is a major risk factor for developing OSAS. However, OSAS has been associated with hormonal and metabolic alterations that could predispose patients to obesity. The aim of this study was to investigate the independent role of apneas and obesity on plasma levels of metabolic hormones (adiponectin, ghrelin, and leptin) in patients with OSAS. We have studied patients with OSAS and controls with and without obesity. All patients were male, had an apnea-hypopnea index of 20/h or greater, and were eligible for nasal continuous positive airway pressure (nCPAP) treatment. Patients were considered obese (n = 28) when their BMI was higher than 30 kg/m(2) and non-obese (n = 21) when it was lower than 27 kg/m(2). Non-obese control subjects (n = 20) were non-snorers with a normal cardiorespiratory sleep study, while obese control subjects (n = 10) were recruited from those obese subjects who were visited in our sleep unit and for whom OSAS was excluded by full polysomnography. A single blood sample was obtained from an antecubital vein in all participants after the completion of the nocturnal sleep laboratory recording. Plasma leptin, adiponectin, and ghrelin levels were determined by radioimmunoassay. The adiponectin, ghrelin, and leptin plasma levels were similar in both patients and controls. There were differences in leptin and adiponectin plasma levels between the obese and non-obese in both patient and control groups. In the case of ghrelin, differences between obese and non-obese subjects were only seen in patients. There were no significant differences in hormone levels between the obese controls and obese patients or between non-obese controls and non-obese patients. After 3 months of nCPAP treatment, adiponectin levels decreased significantly both in obese and non-obese patients, and leptin levels decreased in obese patients. Finally, nCPAP did not reduce ghrelin in either obese or non-obese patients. The basal levels of leptin, adiponectin, and ghrelin were mostly associated with obesity. We found that sleep apnea was not a determinant factor in leptin, adiponectin, and ghrelin hormonal levels. Interestingly, nCPAP treatment diminishes leptin in obese OSA patients and adiponectin levels in obese and non-obese patients with OSAS.

Comparison of Propranolol and Sotalol Pharmacokinetics in Obese Subjects

Six obese subjects (mean +/- s.d. : 145.1 +/- 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (+/-)-propranolol base (0.108 mg kg-1 of ideal body weight) or of (+/-)-sotalol base (1.06 mg kg-1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non-obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 +/- 2.9 L h-1; volume of distribution during the terminal phase = 79.8 +/- 19.8 L or 0.9 +/- 0.2 L kg-1; terminal half-life = 6.2 +/- 1.6 h). For propranolol, total clearance (44.3 +/- 15.9 L h-1) and volume of distribution (230.5 +/- 48.2 L or 2.7 +/- 0.7 L kg-1) were significantly less than control values. The terminal half-life (3.9 +/- 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.

Hedonic hunger is increased in severely obese patients and is reduced after gastric bypass surgery

Overeating as a pathogenetic hallmark of obesity may be promoted by an increase in hedonic hunger, ie, the drive to eat palatable foods in the absence of energy need. Gastric bypass surgery, which effectively reduces severe obesity, might also affect hedonic hunger. The objective was to assess hedonic hunger in severely obese patients with and without a history of gastric bypass surgery. Severely obese patients who had not undergone gastric bypass surgery (n = 123), gastric bypass patients (n = 136), and nonobese control subjects (n = 110) were examined with the Power of Food Scale (PFS)--a questionnaire that reliably measures an individual's motivation to consume highly palatable foods. Compared with nonobese control subjects, severely obese patients achieved markedly higher aggregated PFS scores and subdomain scores related to generally available as well as physically present foods (all P < 0.001). On the aggregated score as well in those 2 subdomains, gastric bypass patients scored significantly lower than did non-gastric bypass obese patients (all P < 0.001) and did not differ significantly from the nonobese control group (P > 0.2). In contrast, in the PFS domain concerning food tasted, gastric bypass patients had significantly lower scores than did the nonobese control subjects (P = 0.04) and the severely obese patients (P = 0.008), both of whom did not differ significantly in this measure (P = 0.90). In comparison with nonobese control subjects, severely obese patients display a marked increase in hedonic hunger that is not observed in patients who have undergone gastric bypass surgery, suggesting that the operation normalizes excessive appetite for palatable foods, which may be an important pathophysiologic feature of severe obesity.

Obesity and Sleep: A Bidirectional Association?

Obesity and Sleep: A Bidirectional Association?

Routine MRI findings of the asymptomatic foot in diabetic patients with unilateral Charcot foot

BackgroundImaging studies of bones in patients with sensory deficits are scarce.AimTo investigate bone MR images of the lower limb in diabetic patients with severe sensory polyneuropathy, and in control subjects without sensory deficits.MethodsRoutine T1 weighted and T2-fat-suppressed-STIR-sequences without contrast media were performed of the asymptomatic foot in 10 diabetic patients with polyneuropathy and unilateral inactive Charcot foot, and in 10 matched and 10 younger, non-obese unmatched control subjects. Simultaneously, a Gadolinium containing phantom was also assessed for reference. T1 weighted signal intensity (SI) was recorded at representative regions of interest at the peritendineal soft tissue, the tibia, the calcaneus, and at the phantom. Any abnormal skeletal morphology was also recorded.ResultsMean SI at the soft tissue, the calcaneus, and the tibia, respectively, was 105%, 105% and 84% of that at the phantom in the matched and unmatched control subjects, compared to 102% (soft tissue), 112% (calcaneus) and 64% (tibia) in the patients; differences of tibia vs. calcaneus or soft tissue were highly significant (p < 0.005). SI at the tibia was lower in the patients than in control subjects (p < 0.05). Occult traumatic skeletal lesions were found in 8 of the 10 asymptomatic diabetic feet (none in the control feet).ConclusionMR imaging did not reveal grossly abnormal bone marrow signalling in the limbs with severe sensory polyneuropathy, but occult sequelae of previous traumatic injuries.

Effects of Isolated Obesity on Left and Right Ventricular Function: A Tissue Doppler and Strain Rate Imaging Study

To determine the subclinical effects of isolated obesity and its duration on cardiac function by using routine echocardiography and tissue Doppler myocardial strain rate. Forty-nine subjects were enrolled in this study; 29 with isolated obesity defined as a body mass index > or = 30 kg/m(2) with no other cardiovascular comorbidities, and 20 nonobese controls. All subjects underwent two-dimensional and Doppler echocardiography including tissue Doppler imaging and myocardial strain rate. The average duration of obesity was 12.1 years (4-18 years). Abnormalities of left ventricular (LV) wall thickness, mass, diastolic function, and left atrial size were detected in obese individuals, despite having preserved ejection fractions. The LV global longitudinal peak strain rate was significantly lower in obese subjects compared to nonobese control subjects (1.07 +/- 0.14 vs. 1.38 +/- 0.12, P < 0.001). Using multivariate analysis, the duration of obesity (ss=-0.76, P < 0.001), body mass index (ss=-0.35, P = 0.023), and age (ss=-0.29, P = 0.009) were independent predictors of the decreased LV global longitudinal peak strain rate, while the duration of obesity (ss=-0.66, P < 0.001) and body mass index (ss=-0.28, P = 0.037) were independent predictors of the decreased right ventricular (RV) peak strain rate. The presence and the duration of obesity were associated with impairment of subclinical biventricular systolic and diastolic function. These findings have the potential to increase awareness of subclinical cardiac manifestations in patients with isolated obesity and influence their early management.

Study on adiponectin levels in non-obese first-degree relatives of patients with type 2 diabetes

Objective To investigate the adiponectin levels in non-obese first-degree relatives (FDR)of type 2 diabetic subjects and its relation to insulin sensitivity and the intima-media thickness of the common carotid artery (IMT) during 5-year follow-up. Methods Fifty-three FDR subjects and 37 control subjects who were free of type 2 diabetes were enrolled. Plasma adipenectin, lipid profile, blood glucose, fasting insulin, and blood pressure were determined at baseline and after 5-year follow-up. IMT and endothelial-dependent vasodilation (EDVD) were measured by high-resolution B-mode ultrasound imaging. Homeostasis model assessment was used to evaluate insulin resistance (HOMA-IR)and β-cell function (HOMA-β). 29 FDR subjects and 20 control subjects completed the follow-up. Results Comparing with the control, plasma adiponectin levels in non-obese FDR subjects were lower at baseline [(10.06±5.79)vs (14.43±7.91) mg/L, P< 0.05]. Plasma adiponectin were decreased 24.0% in non-obese FDR and 36.7% in control duning 5 year follow-up (both P<0.05). Adiponectin levels were negatively correlated with waist-to-hip ratio (r = -0. 397), fasting blood glucose (r = -0. 373), IMT (r = -0. 372), and HOMA-IR (r=-0. 40)in the non-obese FDR. After adjusting other relevant risk factors,adiponectin was associated with age, high-density lipoprotein-cholesterol, and IMT in multiple regression analyses in non-obese FDR group. In the control group, a similar analysis revealed that low-density lipoprotein-cholesterol and IMT explained 25% of the variability in the adiponectin concentration. Conclusion Plasma adiponectin levels were decreased after 5 years in both non-obese FDR and control subjects. Decreased adiponectin level may be related to IMT increment. Key words: Diabetes mellitus,type 2 ; Adiponectin; Intima-media thickness of the common carotid artery

Leptin receptor 170 kDa (OB‐R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance

To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin signalling and signal transducer and activator of transcription 3 (STAT3) phosphorylation and reduce AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) phosphorylation. Deltoid and vastus lateralis muscle biopsies were obtained from 20 men: 10 non-obese control subjects (mean +/- s.d. age, 31 +/- 5 years; height, 184 +/- 9 cm; weight, 91 +/- 13 kg; and percentage body fat, 24.8 +/- 5.8%) and 10 obese (age, 30 +/- 7 years; height, 184 +/- 8 cm; weight, 115 +/- 8 kg; and percentage body fat, 34.9 +/- 5.1%). Skeletal muscle OB-R170 (OB-R long isoform) protein expression was 28 and 25% lower (both P < 0.05) in arm and leg muscles, respectively, of obese men compared with control subjects. In normal-weight subjects, SOCS3 protein expression, and STAT3, AMPKalpha and ACCbeta phosphorylation, were similar in the deltoid and vastus lateralis muscles. In obese subjects, the deltoid muscle had a greater amount of leptin receptors than the vastus lateralis, whilst SOCS3 protein expression was increased and basal STAT3, AMPKalpha and ACCbeta phosphorylation levels were reduced in the vastus lateralis compared with the deltoid muscle (all P < 0.05). In summary, skeletal muscle leptin receptors and leptin signalling are reduced in obesity, particularly in the leg muscles.

Effect of exercise training on A‐FABP, lipocalin‐2 and RBP4 levels in obese women

Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers. Thirty obese Korean women and 15 age-matched nonobese control subjects were studied. Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week. Obese women exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4 microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme. Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.

Differential Changes in Dietary Habits after Gastric Bypass Versus Gastric Banding Operations

Reduction of food intake is an important mechanism by which bariatric procedures reduce body weight. However, only few studies have systematically assessed what patients actually eat after different types of bariatric operations. Dietary habits were assessed by a food frequency questionnaire in 121 bariatric patients (48 gastric bypass patients, 73 gastric banding patients) during follow-up visits in our interdisciplinary obesity center as well as in 45 severely obese (body mass index (BMI)>35 kg/m2) and 45 nonobese (BMI<27 kg/m2) control subjects. As compared with nonobese control subjects, obese control subjects consumed more meat, white bread, and diet soft drinks. Gastric bypass patients showed an enhanced consumption of foods rich in protein such as poultry, fish, and eggs as well as of cooked vegetables, while the consumption of fatty sweets like chocolate, cake, biscuits, and cookies was found to be distinctly reduced in this patient group. In contrast, gastric banding patients reported on a reduced intake of pasta, white bread, and fresh fruits and, just like gastric bypass patients, also on an enhanced intake of poultry and fish. Direct comparison of dietary habits between the two bariatric patient groups revealed that gastric bypass patients consumed more frequently fresh fruits, eggs, and diet soft drinks but strikingly less chocolate than gastric banding patients. Collectively, data clearly point to distinct changes in dietary habits after bariatric operations which markedly differ between gastric bypass and gastric banding patients. Overall, it is tempting to conclude that gastric bypass operations lead to a healthier and a more balanced diet than gastric band implantations.

Upper Gastrointestinal Symptoms and Associated Disorders in Morbidly Obese Patients: A Prospective Study

To prospectively evaluate the frequency of upper gastrointestinal symptoms and associated disorders in morbidly obese patients with endoscopy and histology prior to their gastric bypass surgery in comparison with age- and sex-matched nonobese control subjects. All patients who were scheduled to undergo laparoscopic gastric bypass for treatment of morbid obesity (body mass index, BMI > 40 kg/m(2)) during a 1-year period (n = 101) were included in the study. Age- and sex-matched nonobese patients who were seen in the medical clinics during the study period were enrolled as control subjects. The demographic data, total body weight, body mass index, and gastrointestinal symptoms were recorded, and the results of upper endoscopy and histology were tabulated. Endoscopic documentation of hiatal hernia, esophagitis, gastritis, gastric polyps, and peptic ulcer disease was also noted along with the histologic findings of the mucosal biopsies from the upper gastrointestinal tract. The prevalence of heartburn as a symptom was significantly higher (P < 0.05) in the morbidly obese patients (32.6%) compared with in the control group (18.8%). Endoscopically, the prevalence of hiatal hernia was also significantly higher (P < 0.05) in the morbidly obese group (38.6%) compared with in the control group (13.8%). Similarly the frequency of endoscopically and histologically identified gastritis was significantly higher (P < 0.01) in the morbidly obese patient group. However, the frequency of histologically identified Helicobacter pylori was not statistically different in the two groups. These observations suggest a significant increase in the frequency of heartburn, hiatal hernia, and histologically identified gastritis in morbidly obese patients.

Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees.

OBJECTIVE— Melanocortin-4 receptor (MC4R) deficiency is the most frequent genetic cause of obesity. However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation carriers is unknown.RESEARCH DESIGN AND METHODS— We determined the MC4R sequence in 2,257 obese individuals and 2,677 nonobese control subjects of European origin and established the likely functional impact of all variants detected. We then included relatives of probands carriers and studied 25 pedigrees, including 97 carriers and 94 noncarriers from three generations.RESULTS— Of the MC4R nonsynonymous mutations found in obese subjects, 68% resulted in a loss of function in vitro. They were found in 1.72% of obese versus 0.15% of nonobesed subjects (P = 6.9 × 10−10). Among the families, abnormal eating behavior was more frequent in both MC4R-deficient children and adults than in noncarriers. Although BMI was inversely associated with educational status in noncarrier adults, no such relationship was seen in MC4R mutation carriers. We observed a generational effect, with a penetrance of 40% in MC4R-deficient adults aged >52 years, 60% in 18- to 52-year-old adults, and 79% in children. The longitudinal study of adult carriers showed an increasing age-dependent penetrance (37% at 20 years versus 60% at >40 years).CONCLUSIONS— We have established a robust estimate of age-related penetrance for MC4R deficiency and demonstrated a generational effect on penetrance, which may relate to the development of an “obesogenic” environment. It remains to be seen whether appropriate manipulation of environmental factors may contribute to preventing the development of obesity even in those strongly genetically predisposed to it.