Markers In Obese Subjects Research Articles

Association of pro-inflammatory cytokines, inflammatory proteins with atherosclerosis index in obese male subjects.

Investigation the association of pro-inflammatory markers interleukin (IL)-1β and IL- 10 expression, serum levels of C-reactive protein (CRP), cyclooxygenase-2 (COX2), High-density lipoprotein (HDL), Apolipoprotein A1 (ApoA1), and ATP Binding Cassette Subfamily A Member 1 (ABCA1) inflammatory proteins with atherosclerosis index (homocysteine) in normal-weight and obese male subjects. 59 males including 30 obese (Body mass index (BMI) of≥30kg/m2) and 29 normal-weight (BMI of 18.5-24.9kg/m2) were joined to this study. Plasma levels of IL-1β and IL-10 (pg/mL), CRP (pg/mL), COX-2 (ng/mL), APOA1 (mg/dL), ABCA1 (ng/mL), HDL, Cholesterol, and Triglyceride (TG) (mg/dL), and homocysteine (µmol/L) was measured. Association of these biomarkers with homocysteine was determined. Obese subjects had higher serum levels of IL10, IL1β, CRP, COX-2, TG, and cholesterol concentrations (allp<0.05 except IL-10 and cholesterol) and low levels of HDL, APOA1, and ABCA1 (non-significant differences) in comparison to normal-weight group. Homocysteine levels were high in obese men with no significant differences between the two groups. In obese subjects, homocysteine had a significant inverse correlation with APOA1, ABCA1, and HDL, and a strong and moderate positive correlation was found with CRP and TG levels, respectively. High level of homocysteine and its correlation with inflammation proteins and markers in obese subjects appear to be contributed with atherosclerosis development.

Association between serum netrin-1 level and obesity-related markers in obese subjects

Netrins are important signaling proteins that guide both neural and vascular development. Netrin-1 regulates many physiological processes such as cell proliferation, adhesion and migration. The aim of this study was to determine the association between serum netrin-1 level and biochemical parameters in obese subjects. Serum samples were collected from obese (n=15) and control (n=30) subjects. The serum netrin-1 levels were evaluated by ELISA. Variable data were compared by Mann Whitney U test and correlation was estimated by Spearman correlation analyses. The level of circulating netrin-1 protein was determined to be significantly lower in obese group compared to controls. The median value was 844.0 pg/mL in the control group and 338 pg/mL in the obese group (p

Effects of Vitamin D Status on Inflammatory Markers in Obese Subjects: A Systematic Review

Background: Recent studies have demonstrated the role of micronutrients in the manifestation of comorbidities associated with obesity. Vitamin D deficiency, in particular, appears to be associated with increased levels of inflammatory markers, which may lead to chronic low-grade inflammation, elevating the risk of chronic diseases such as diabetes, metabolic syndrome, and cardiovascular disease. The objective of this study was to perform a systematic review of observational studies conducted to investigate the effect of vitamin D deficiency on inflammatory markers in obese subjects. Methodology: This systematic review was conducted in accordance with the “STROBE” and PRISMA recommendations. Observational studies that evaluated the effect of vitamin D status on inflammatory markers in obese subjects were selected and reviewed. Searches were conducted in the PubMed, SciVerse Scopus, and Web of Science databases from February 21 to 22, 2018. Results: After the selection and removal of duplicate articles, 10 eligible articles were identified. Results from eight observational studies showed an association between vitamin D deficiency or insufficiency in the body and increased concentrations of inflammatory markers in obese individuals. On the other hand, two of the studies did not demonstrate any correlation. With regard to the inflammatory markers evaluated, eight studies showed high concentrations of ultra-sensitive C-reactive protein, five studies found an increase in interleukin-6 concentrations, and two studies noted increased levels of tumor necrosis factor. Conclusion: The data presented in this systematic review provide evidence of the association between vitamin D deficiency and increased inflammation in obesity.

Crosstalk between Oxidative Stress and Inflammation in Obesity

Obesity is a multifactorial disease in which oxidative stress and inflammation play important roles. The aim of our study was to evaluate oxidative stress levels and inflammation markers in obese subjects vs. controls and to investigate the relationship between these values. We found increased levels of reactive oxygen species and inflammation markers (fibrinogen, ferritin, CRP, NLR) and decreased levels of antioxidants in obese subjects vs. controls.

The Association Between Serum Vaspin and Omentin-1 Levels in Obese Children with Metabolic Syndrome.

Excess visceral fat accumulation results in altered release of adipokines. The aim of this study was to examine the relationship between new adipokines (omentin-1 and vaspin), insulin resistance, and serum inflammatory markers in obese subjects with metabolic syndrome (MS). The study included a total of 121 obese children (79 females and 42 males, aged 12-17 years old). The obese subjects were divided into two groups based on the presence or absence of MS criteria (MS group and non-MS group). Serum omentin-1, vaspin, and high-sensitivity C-reactive protein (CRP) were measured in addition to the other glucose metabolism parameters. MS was diagnosed in 45 obese children and 76 children did not meet the MS criteria. Serum omentin-1 (289.5 ± 51.9 ng/mL vs. 268.2 ± 60 ng/mL, P = 0.03) levels were significantly lower in the MS group compared to the non-MS group. Serum vaspin levels (1058.3 ± 118 pg/mL vs. 1178.6 ± 158 pg/mL, P = 0.02) were higher in the MS group than the non-MS group. CRP levels correlated well with both the adipokines (r = -0.236, P = 0.04 for omentin-1 and r = 0.296, P = 0.008 for vaspin), although these adipokines did not show statistically significant correlations with fasting glucose-insulin levels, homeostasis model assessment of insulin resistance, and 2 hr postload glucose level. Higher vaspin and lower omentin-1 levels were determined in obese MS children compared to non-MS children and these adipokines were significantly correlated with high CRP values. These data support the view that adipokines in MS children contribute to increased inflammation markers before abnormal glucose metabolism.

Relation of the protein glycation, oxidation and nitration to the osteocalcin level in obese subjects

Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies had shown that treatment of osteoblast-like cells with advanced glycation end product-modified bovine serum resulted in reduced synthesis of collagen 1 and osteocalcin. The aim of this study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration, as well as pro-inflammatory and antioxidant defense markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m; n=34)] and obese subjects (30<BMI <40 kg/m2; n=98), both sexes, aged 25 to 65 years, were included in this study. Urinary glycation, oxidation and nitration free adduct concentrations were determined by stable isotopic dilution analysis liquid chromatography and mass spectrometry, and normalized to creatinine. Obese subjects had lower Gla-OC serum levels when compared to the non-obese controls. Obese subjects had increased serum concentrations of insulin, C reactive protein, interleukin 6, leptin and insulin resistance index (HOMA IR). Urinary early glycation and advanced glycation end product (AGE) free products, Nε-fructosyl-lysine and 3-deoxyglucosone-derived hydroimidazolone, respectively, and oxidative damage marker, N-formylkynurenine free adduct, were increased in the obese compared to the non-obese subjects. Serum Gla-OC was negatively correlated with urinary methylglyoxal-derived AGE, hydroimidazolone MG-H1, and N-formylkynurenine free adducts. The Gla-OC/Glu-OC index negatively correlated with the MG-H1 free adduct, and correlated positively with the antioxidant defense marker - the glutathione peroxidase activity. Our results suggest that increased AGEs and protein oxidative damage markers in the course of obesity may contribute to decreased Gla-OC level and, consequently, future risk of decreased bone formation.

Role of omentin-1 and C-reactive protein in obese subjects with subclinical inflammation

BackgroundWhile chronic subclinical inflammation is now considered to be a predisposing risk factor of cardiovascular diseases, the extent by which adipokines induce metabolic abnormalities in humans is not fully resolved. The purpose of this study was to examine the relationship between insulin resistance and serum inflammatory markers in obese subjects. MethodsOne hundred and five subjects without any clinically evident CVD were classified into 3 coronary risk levels according to Framingham risk score. Demographic and anthropometric variables were estimated. Serum levels of lipid profile, blood glucose, insulin, omentin-1 and high sensitivity-C reactive protein (hs-CRP) were measured in fasting blood samples. Insulin resistance indices were also calculated. Results29% and 62% of the study population were overweight and obese respectively by body mass index (BMI) measures. Almost half of the study population was considered diabetic. There was a tendency for a fall in serum omentin-1 concentrations with increasing coronary risk with a significant increase in hs-CRP levels in the same direction (p < 0.05). Age and fasting blood glucose were found to be independently associated with serum omentin-1 levels. BMI and fasting blood glucose were independent determinants of serum hs-CRP levels. ConclusionsOmentin-1 might be associated with the development of diabetes mellitus indirectly via insulin activity and obesity. These findings may have important implications for the pathophysiology and therapy of diabetes mellitus by further longitudinal studies.

MicroRNA-125a-3p expression in abdominal adipose tissues is associated with insulin signalling gene expressions in morbid obesity: observations in Taiwanese.

Micro (mi) RNAs have been found to play an important role in the regulation of adipogenesis and insulin sensitivity. However, associations between miRNA and insulin signalling-related gene expressions in abdominal adipose tissues in obese subjects remain unclear. We used a microarray platform to screen miRNA expressions in abdominal adipose tissues between genders in severely obese subjects and found that the top-ranking miRNA in abdominal omental adipose tissues was miRNA-125a-3p. MicroR-125a-3p and insulin signalling-related gene expressions in abdominal omental adipose tissues of all subjects (11 men and 10 women) were subsequently quantified by a real-time PCR. Also, associations of miR-125a-3p with insulin signalling-related gene expression and biochemical markers in obese subjects were analyzed by a linear regression analysis. miR-125a-3p expressed by abdominal omental adipose tissues was much higher in obese men than women. No gender difference was observed in abdominal subcutaneous adipose tissues. Concomitant with high miR-125a-3p, c-Jun N-terminal kinase gene expression was also higher, whereas insulin receptor was lower in men than women. There were negative associations of miR-125a-3p with the insulin receptor and phosphatidylinositol 3-kinase expressions. Fasting plasma glucose and cholesterol levels were positively associated with miR- 125a-3p expression. These associations were obvious in obese men but not women. Our results support the involvement of miR-125a-3p in regulating the insulin signalling pathway and imply that increased miR- 125a-3p expression in omental adipose tissues may be a characteristic feature of insulin resistance in obese men.

Impact on Some Antioxidant Enzymes and Vitamins in Obese Adolescents of North West Indians

Obesity is one of the most common health problems in developed and developing nations such as India. In India, prevalence of obesity among adolescents is 6-24 %. In addition, obesity is considered as one of the risk factors for the initiation of many chronic diseases. Oxidative Stress (OS) is a well-established hallmark of diseases such as diabetes mellitus, cancer, and cardiovascular diseases. The aim of the study was to evaluate OS markers in obese subjects with respect to normal healthy subjects. The present case-control study was carried out on 25 male obese adolescent children with body mass index (BMI) ≥25 kg/m2 and on equal number of male normal healthy children with BMI<15 kg/m2 in the age range of 10-19 years. These subjects were recruited from rural and urban areas of Amritsar District, Punjab, India. The levels of malondialdehyde (MDA), antioxidant enzymes/molecules such as superoxide dismutase (SOD), reduced glutathione (GSH), Glutathione Reductase (GR), Glutathione Peroxidase (GPx), antioxidant Vitamin E and Vitamin C, and β-carotene along with total antioxidant activity (TAA) were evaluated. Significant increase in the concentration of MDA by 114.81% was observed in obese adolescents in comparison to normal healthy adolescents while a significant fall was observed in SOD (47.153%), GSH (60.79%), GR (43.39%), GPx (29.92%), TAA (54.08%), Vitamin E (45.45%), Vitamin C (56.14%), and β-carotene (32.88%) levels in obese adolescents as compared to normal healthy control adolescents. Aforementioned observations suggested that OS induced in the obese adolescents even in the absence of any chronic diseases. Therefore, obesity should be treated at the early stages to prevent further complications.

Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: A randomized placebo controlled trial

BackgroundCaloric restriction and n-3 polyunsaturated fatty acid (PUFA) supplementation protect from some of the metabolic complications. The aim of this study was to assess the influence of a low calorie diet with or without n-3 PUFA supplementation on glucose dependent insulinotropic polypeptide (GIP) output and insulin sensitivity markers in obese subjects. MethodsObese, non-diabetic subjects (BMI 30–40kg/m2) and aged 25–65yr. were put on low calorie diet (1200–1500kcal/day) supplemented with either 1.8g/day n-3 PUFA (DHA/EPA, 5:1) (n=24) or placebo capsules (n=24) for three months in a randomized placebo controlled trial. Insulin resistance markers and GIP levels were analysed from samples obtained at fasting and during an oral glucose tolerance test (OGTT). ResultsCaloric restriction with n-3 PUFA led to a decrease of insulin resistance index (HOMA-IR) and a significant reduction of insulin output as well as decreased GIP secretion during the OGTT. These effects were not seen with caloric restriction alone. Changes in GIP output were inversely associated with changes in red blood cell EPA content whereas fasting GIP level positively correlated with HOMA-IR index. Blood triglyceride level was lowered by caloric restriction with a greater effect when n-3 PUFA were included and correlated positively with fasting GIP level. ConclusionsThree months of caloric restriction with DHA+EPA supplementation exerts beneficial effects on insulin resistance, GIP and triglycerides. General significanceCombining caloric restriction and n-3 PUFA improves insulin sensitivity, which may be related to a decrease of GIP levels.

OP0163 Weight loss and induction of minimal disease activity in psoriatic arthritis patients starting TNF-α blockers treatment

BackgroundPsA patients exhibit an increased prevalence of obesity. By leading to an abnormal expression of “adipokines” (TNF-α, IL-6, leptin, adiponectin), obesity determines a pro-inflammatory status. Thus, an interaction between obesity-related...

Effect of combined thermal and electrical muscle stimulation on cardiorespiratory fitness and adipose tissue in obese individuals

To better understand how prolonged electrical muscle stimulation can improve cardiorespiratory risk markers in obese subjects, we investigated the effect of prolonged combined thermal and electrical muscle stimulation (cTEMS) on peak oxygen consumption (VO2peak) and body composition with subsequent lipolytic and mitochondrial activity in adipocytes. Eleven obese (BMI ≥ 30 kg/m(2)) individuals received cTEMS in three 60-minute sessions per week for 8 weeks. Activity levels and dietary habits were kept unchanged. Before and after the stimulation period, functional capacity was assessed by VO2peak, and body composition was analysed. Lipolytic activity was determined in abdominal adipose tissue by 24 hours of microdialysis on a sedentary day, and adipose tissue biopsies were taken for the gene expression analysis. Eight weeks of cTEMS significantly increased VO2peak from 28.9 ± 5.7 to 31.7 ± 6.2 ml/kg/min (p < 0.05), corresponding to an average increase of 1.2% per week. Oxygen uptake and work capacity also increased at the anaerobic threshold. Mean microdialytic glycerol concentration over 24 hours, an index of sedentary lipolytic activity, increased from 238 ± 60 to 306 ± 55 µM (p < 0,0001), but no significant changes in body composition were observed. In addition, PGC-1α and carnitine-palmitoyltransferase-2 mRNAs were significantly upregulated in subcutaneous abdominal adipose tissue. In obese individuals with unchanged lifestyles, 8 weeks of cTEMS significantly improved functional capacity towards a higher fatigue resistance. This increase also gave rise to elevated lipolytic activity and increased mitochondrial activity in abdominal adipose tissue.

P042 Multiplexed analysis of inflammatory, metabolic and stress markers in obese subjects before and after a defined exercise program

Introduction Obesity is characterized by a chronic-low grade inflammation and aberrant regulation of various forms of stress response in key metabolic sites. The white adipose tissue has been identified as the predominant site of obesity-associated inflammatory reactions, which are triggered as a consequence of immune cells infiltration. Physical exercise has been widely recognized for treating obesity and metabolic syndromes. The objectives of this study are: (1) To investigate the release pattern of pro- and anti-inflammatory mediators in obese participants, (2) To evaluate the effect of a defined exercise protocol on their release into the circulation, (3) To correlate their expression with the metabolic and stress markers. Methods A total of 600 healthy individuals divided into 3 groups using the body mass index as a reference (lean, overweight and obese) are being enrolled in a 6-month defined exercise protocol. Blood samples and abdominal subcutaneous adipose biopsies are collected at baseline (t0) and after 3 (t3) and 6 (t6) months of exercise. Plasma cytokine and metabolic markers levels were assessed simultaneously using the xMAP multiplex immunobead assay technology (Bioplex). Markers of the oxidative stress, namely ROS and TBARS were measured on plasma or serum using commercially available kits. Gene expression profile was done by RT-PCR using RT-profiler- array kits consisting of the heat shock protein panel, obesity panel and the oxidative stress panel. Western blotting and immunohistochemistry techniques were used to validate the gene expression data. Statistical analyses were performed using SAS software. Results The analysis carried out on a first set of samples indicated significant release of RANTES in obese individuals compared to lean participants ( P Conclusion Our result demonstrated a differential expression of RANTES chemokine in obese participants in comparison to lean control and highlighted its roles in obesity. Exercise was able to restore the normal expression of RANTES. The existence of a negative correlation between RANTES expression and the metabolic and stress responses is suggestive of a pathological role of RANTES and may be considered a potential therapeutic target.

Effects of Auricular Acupuncture on Anthropometric, Lipid Profile, Inflammatory, and Immunologic Markers: A Randomized Controlled Trial Study

A randomized controlled clinical trial was performed to examine the effectiveness of auricular acupuncture on body weight loss and its impact on lipid profile, and immunologic and inflammatory markers in obese subjects. Participants (n=204) were randomized to therapeutic acupuncture and control groups. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks (first period) in combination with a low-calorie diet. In the next 6 weeks (second period), the low-calorie diet was used on its own. Subjects were assessed at the beginning and 6 and 12 weeks later. In addition to anthropometric and lipid parameters, serum anti-heat shock protein (Hsp)-27, 60, 65, 70 and high sensitive C-reactive protein (hs-CRP) levels were assessed. In the first period, anthropometric parameters and hs-CRP changed significantly in both groups, while significant changes in anti-Hsp antibodies were only observed in case subjects. In the second period, which shows the sustainable effects of acupuncture, changes in anthropometric parameters were more prominent in controls, while significant reductions in the group receiving authentic acupuncture were maintained for anti-Hsp antibodies. A comparison between the first and second period in both groups showed that the changes for most of the parameters were more significant in the first period. Comparison between cases and controls showed that authentic acupuncture was more effective in reducing the levels of anthropometric factors and anti-Hsp antibodies but not hs-CRP. Auricular acupuncture in combination with diet restriction was effective for weight loss and dyslipidemia. Moreover, it was found that it has immunomodulatory but not anti-inflammatory effects on the immune system by regulation of the levels of anti-Hsp antibodies.

Platelet activation in the pathogenesis of obesity and vascular disease

The pathogenesis of atherosclerotic disease is complex, and very topical, as clearly highlighted in a recent position paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology in this journal, which deals with atherosclerotic plaques and their ‘stabilisation’ per se (1). A number of associations have been observed between lipid abnormalities, markers of metabolic syndrome and platelet activation (1–5). In recent years, many studies have explored associations for platelet activation markers to gain insights on the pathogenesis of obesity and atherosclerotic disease (6–13). In this issue of Thrombosis and Haemo stasis, Csongradi et al. report on a large cross-sectional cohort study that explored relationships for platelet activation markers in obese subjects, including those with and without common co-morbidities for atherosclerotic disease (14). Key findings of their study were that platelet and plasma P-selectin levels, and the plasma levels of platelet microparticles, were associated with carotid intimal medial thickness and a variety of other vascular risk factors, including fasting plasma glucose, insulin levels and triglycerides (14). These observations imply that the extent of atherosclerotic disease, and the metabolic derangements associated with obesity and atherosclerotic disease, influence the generation of platelet microparticles. This possibility is supported by a recent study that showed weight loss-induced improvements in insulin resistance, among women with obesity, reduced markers of platelet activation (6). While association studies cannot determine causation, they are important to developing new hypotheses on the pathogenesis of atherosclerotic disease. Platelet microparticles have attracted much interest both experimentally and clinically (15–19). Indeed, given their significant procoagulant activity (18, 19), their elevation in pathogenic states could contribute to the progression of vascular disease and acute thrombotic events. Nonetheless, uncertainties remain about whether observed associations between elevated levels of platelet-derived microparticles with prothrombotic, metabolic and inflammatory parameters are correlative or causative, and how much platelet microparticle generation, and other aspects of platelet activation, contribute to the pathogenesis of atherosclerotic disease in obese individuals. The “independent” associations that Csongradi et al. found between platelet-derived microparticle levels with body mass index, and between soluble P-selectin and fibrinogen, and platelet P-selectin and both carotid intimal medial thickness and PAI-1 (14) provide further evidence that platelet activation is influenced by the complex metabolic and inflammatory parameters that participate in the pathogenesis of atherosclerotic disease. Despite these advances, uncertainties still remain about whether measuring platelet activation markers has a role in diagnostic or therapeutic decision making for obese and non-obese individuals who have or do not have evidence of atherosclerotic disease. This still remains an exciting and expanding field of research.

High Plasma Phospholipase A2 Activity, Inflammation Markers, and LDL Alterations in Obesity With or Without Type 2 Diabetes

Plasma phospholipases A(2) (PLA(2)) hydrolyze phospholipids of circulating lipoproteins or deposited in arteries producing bioactive lipids believed to contribute to the atherosclerotic inflammatory response. PLA(2)(s) are elevated in obesity and type 2 diabetes (T2D) but it is not clear which of these conditions is the cause since they frequently coexist. This study attempts to evaluate if high plasma PLA(2)(s) activities and markers of their effects in lipoproteins are associated with obesity or T2D diabetes, or with both. Total PLA(2) and Ca(2+)-dependent and -independent activities, lipids, lipoproteins, apoAI, and apoB apolipoproteins and affinity of apoB-lipoproteins for arterial proteoglycans were measured, as well as Inflammation markers. These parameters were evaluated in plasma samples of four groups: (i) apparently healthy controls with normal BMI (nBMI), (ii) obese subjects with no T2D, (iii) patients with T2D but with nBMI, and (iv) obese patients with T2D. PLA(2) activities were measured in the presence and absence of Ca(2+) and in the presence of specific inhibitors. Obese subjects, with or without T2D, had high activities of total PLA(2) and of Ca(2+)-dependent and Ca(2+)-independent enzymes. The activities were correlated with inflammation markers in obese subjects with and without diabetes and with alterations of low-density lipoproteins (LDLs) that increased their affinity for arterial proteoglycans. Ca(2+)-dependent secretory (sPLA(2)) enzymes were the main responsible of the obesity-associated high activity. We speculate that augmented PLA(2)(s) activity that increases affinity of circulating LDL for arterial intima proteoglycans could be another atherogenic component of obesity.

Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study

The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk. In the EXO group the weight loss was 3.5 kg and in the DIO and DEX groups it was 12 kg in both. Vo(2max) was increased by 14-18% in the EXO and DEX groups with no changes in the DIO group. In the DIO and DEX groups, circulating levels of MCP-1, MIP-1alpha, IL-15, and IL-18 were decreased, and adiponectin was increased (P < 0.05 for all). In the EXO group, MCP-1 was decreased with 10% (P = 0.06). By combining the weight loss in all three groups, we found a correlation between the degree of weight loss and improvement in several of the inflammatory markers (P < 0.05). In AT biopsies, subjects in the DIO and DEX groups achieved a general beneficial but nonsignificant effect on the gene expression of inflammatory markers. In the EXO group, no changes in AT adipokine mRNA were found except for an increment of adiponectin (P < 0.05). In SM, the only observed change was that the gene expression of IL-6 was increased in all three groups (P < 0.05). In conclusion, rather large weight losses (>5-7%) were found to have beneficial effects on circulating inflammatory markers in these obese subjects. Aerobic exercise for 12 wk, which increased Vo(2max), was found to have no effects on circulating inflammatory markers in these obese patients. It is suggested that more intensive exercise may be necessary to affect systemic inflammation.

Discriminated benefits of a Mediterranean dietary pattern within a hypocaloric diet program on plasma RBP4 concentrations and other inflammatory markers in obese subjects

Personalized nutritional strategies to treat obesity may specifically influence inflammatory markers, in addition to reduce body weight. In the present study, we evaluated the effect of a hypocaloric diet based on a Mediterranean dietary pattern (MDP) on nutritional status as well as on plasma concentrations of retinol binding protein-4 (RBP4) and other proinflammatory markers. Fourty-one subjects (24F/17M; age: 37 ± 7 years; BMI: 32.2 ± 3.9 kg/m²) were assigned to follow a MDP within a caloric-restricted diet over an 8-week period. Anthropometrical, clinical, and biochemical variables were measured at baseline and endpoint after the nutritional program. Dietary intervention resulted in a mean weight loss of -4.4 ± 2.5 kg (P < 0.001) and marked reductions (P < 0.05) in plasma concentrations of RBP4, leptin, C-reactive protein, complement C3, and tumor necrosis factor-alpha (TNFα). Individuals with a higher adherence to the MDP during the nutritional intervention presented differentially higher reductions (P < 0.05) in plasma RBP4, IL6, and TNFα. In addition, the increase in the Mediterranean diet score from baseline was a significant and independent predictor factor for the decrease in plasma RBP4 concentration (P < 0.05). In conclusion, our findings suggest that following a hypocaloric diet accompanying a high adherence to a MDP resulted in specific reductions on proinflammatory markers, in addition to a significant improvement in some metabolic syndrome features induced by weight loss, which could be a good combined strategy to treat obesity as well as related metabolic and inflammatory disorders.

The Importance of Brown Adipose Tissue

To the Editor: In the April 9 issue, van Marken Lichtenbelt et al., Cypess et al., and Virtanen et al. report on functioning supraclavicular brown adipose tissue in adult humans. Van Marken Lichtenbelt et al. conclude that brown-adipose-tissue activity induced by exposure to cold is impaired in overweight healthy subjects, and Cypess et al., using epidemiologic-association techniques, conclude that older subjects and those with a higher body-mass index (BMI) have less brown adipose tissue. It is suggested that obesity is associated with reduced brown-adipose-tissue function or activity. However, disseminated brown adipocytes within the large subcutaneous adipose-tissue mass may cumulatively represent substantial brown-adipocyte activity that may not be detected with the use of integrated positron-emission tomography and computed tomography (PET–CT) or crude biochemical studies. Using gene profiling, we found an indication that the brown-adipose-tissue marker uncoupling protein 1 (UCP1) is positively associated with BMI in human subcutaneous adipose tissue (from 33 subjects) (Fig. 1A), as is angiopoietin 2 (ANGP2), a brown-adipose-tissue–enriched angiogenic gene that is a surrogate for F-fluorodeoxyglucose (F-FDG) uptake. Furthermore, cell death–inducing DNA-fragmentation factor (CIDEA), a negative regulator of lipolysis, which is inversely associated with the basal metabolic rate in humans (potentially through indirect UCP1 activation), is reduced in obese subjects matched for glycemic control (Fig. 1B). Such BMI associations are markedly influenced by the presence of diabetes (Fig. 1C and 1D), tempering conclusions about disease drawn from these studies. We have found brown-adipose-tissue markers in obese subjects without diabetes, suggesting that anatomically dispersed brown adipocytes may promote metabolic homeostasis. James A. Timmons, Ph.D.

Inflammatory State and Stress Condition in Weight-lowering Lys109 Arg LEPR Gene Polymorphism Carriers

Carrying variants on the leptin receptor gene (LEPR) may have an impact on inflammatory and stress markers. Thus, the aim of the study was to analyze the role of the Lys109Arg LEPR gene polymorphism on inflammatory (leptin and IL-6) and stress (cortisol) markers in obese subjects who followed a hypocaloric diet designed to lose weight. One hundred and seventy (80 females/90 males) Caucasian subjects (body mass index: 30.8 +/- 2.4 kg/m(2)), were genotyped for the Lys109Arg polymorphism by a PCR/RFLP procedure. Anthropometric measurements were assessed and blood samples were drawn in all the volunteers before and after an 8-week energy-restricted diet (-30% E). Plasma levels of leptin as well as interleukin-6 (IL-6) as proinflammatory markers and circulating cortisol concentrations as a stress hormone were measured. Weight loss (-6.1 +/- 2.7%; p <0.001) induced significant changes in anthropometric and biochemical determinations. The AA genotype group showed a higher fat mass loss as well as greater total cholesterol decrease compared with the minor allele carriers. Moreover, the G allele carriers were associated with a higher basal risk of inflammation (OR = 2.5; p = 0.042) and stress (OR = 3.3; p = 0.011), which were reduced after weight lowering (p >0.05). The Arg allele carriers of the Lys109Arg LEPR gene polymorphism were associated with an increased proinflammatory state and stress condition at baseline. These obesity-related markers were importantly decreased after following a hypocaloric diet.