Leptin Does Not Play a Major Role in Platelet Aggregation in Obesity and Leptin Deficiency

Objective: A recent study suggested that high concentrations of leptin enhance platelet aggregations. Therefore, the aim of this study was to investigate whether platelet aggregation is altered in patients with leptin gene mutations compared with obese subjects or controls. Research Methods and Procedures: Four men (one homozygous man and his three heterozygous brothers) carrying a leptin gene mutation; 20 age‐matched, healthy, unrelated men; and 18 age‐matched obese men were enrolled in the study. Adenosine diphosphate (ADP)‐, collagen‐, and epinephrine‐induced platelet aggregation were evaluated in all individuals. Results: Our results show that patients with the leptin gene mutation (both the homozygous and heterozygous patients) had significantly higher ADP‐induced (78.3 ± 3.4% vs. 57.9 ± 9.3%, p = 0.001), collagen‐induced (78.1 ± 2.9% vs. 56.7 ± 9.3%, p = 0.007), and epinephrine‐induced (76.5 ± 9.2% vs. 59.5 ± 7.70%, p = 0.003) platelet aggregation compared with controls. However, ADP‐, collagen‐, or epinephrine‐induced platelet aggregations were similar to those in obese patients. Platelet aggregation responses to a combination of pretreatment with leptin at concentrations of 20, 50, 100, or 500 ng/mL for 5 minutes and ADP at concentrations of 2 μmol/liter also were evaluated. However, we did not find significant increases in platelet aggregation even at high concentrations of leptin (100 or 500 ng/mL) in leptin‐deficient patients, obese subjects, or controls. Discussion: Our data show that similar to findings in obese humans, homozygous or heterozygous leptin deficiency is associated with increased platelet aggregation compared with controls, and that higher concentrations of leptin do not increase platelet aggregation.     

Comparison of β2-microglobulin serum level between Alzheimer’s patients,cognitive healthy and mild cognitive impaired individuals

Background: Several studies performed in the last years on the brain, showed that beta2-microglobulin (β2m) and MHC can act independently of their canonical immune function to regulate normal brain development, synaptic plasticity and behaviour. Increased systemic levels of soluble β2m have been implicated in cognitive impairments like that associated with chronic haemodialysis, or aortic valve replacement. Increased soluble β2m has also been detected in the cerebral spinal fluid (CSF) of patients with HIV-associated dementia and Alzheimer’s disease (AD).

Objective: To compare plasma β2m levels in healthy subjects and subjects with dementia or cognitive impairment.

Methods: We measured the concentration of β2m in a cohort of 245 individuals and compared sex matched, cognitive healthy individuals.

Results: We found higher levels of β2m in AD patients compared to non-AD MCI and healthy controls (2063?ng/mL ±852 versus 1613?±?503 and 1832?±?382?ng/mL, pp?>?0.05).

Conclusions: Our data confirm that β2m could play a role in AD. However, a replication study in an independent cohort would be necessary to confirm our preliminary results.     

Decreased paraoxonase 2 enzymatic activity in monocyte/macrophages cells. A comparative in vivo and in vitro study for diabetes

Aim: To investigate peripheral blood monocytes/macrophages (Mo/M?) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity.

Methods: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL).

Results: Paraoxonase 2 activity in Mo/M? was significantly lower in type 2 diabetes patients (0.042?±?0.044 vs 0.165?±?0.133U lactonase activity/mg protein in controls, p?1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15–34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S? (to 82?±?18% of the cells incubated with serum, S+) and PON2 activity (from 0.524?±?0.061 in S???to 0.298?±?0.048?U/mg protein). In contrast, when LDL was added, the RB remained lower (61?±?12% of S+, p?=?.03) and PON2 higher (0.580?±?0.030?U/mg protein, p?=?.003).

Conclusions: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.     

Increased plasma concentration of 4-pyridone-3-carboxamide-1-ß-D-ribonucleoside (4PYR) in lung cancer. Preliminary studies

Abstract

4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) is a new nicotinamide derivative, which is potentially toxic to the endothelium. Dysfunction of the endothelium promotes cancer cell proliferation, invasiveness, and inflammatory signaling. The aim of this study was to analyze 4PYR concentration in the plasma of lung cancer patients and its relationship to other known biochemical parameters associated with the endothelium function.

The concentration of 4PYR, nicotinamide, 1-methylnicotinamide (MNA), amino acids, and their derivatives were measured in samples obtained from patients with primary squamous cell carcinoma (n?=?48) and control group (n?=?100).

The concentration of 4PYR and 4PYR/MNA ratio were significantly higher in lung cancer patients as compared to controls (0.099?±?0.009 vs. 0.066?±?0.006?µmol/L and 1.10?±?0.08 vs. 1.97?±?0.15, respectively). The plasma arginine/asymmetric dimethylarginine (Arg/ADMA) ratio was considerably lower in lung cancer patients (253?±?17 vs. 369?±?19) as well as plasma MNA (0.057?±?0.004 vs. 0.069?±?0.003?µmol/L). There was no difference in the plasma concentrations of nicotinamide and nicotinamide riboside in both groups (0.116?±?0.019 vs. 0.131?±?0.014 and 0.102?±?0.006 vs. 0.113?±?0.011, respectively).

In this study, a higher 4PYR concentration was observed for the first time in patients with squamous cell carcinoma. This change may be related to the endothelial dysfunction that promote cancer progression since 4PYR and its derivatives are known to disrupt glycolytic pathway.     

Association of inflammation and cytotoxin-associated gene a positive strains of helicobacter pylori in cardiac syndrome x

Background: Cardiac syndrome X (CSX) is a condition in which patients have the pain of angina despite normal coronary angiogram. Helicobacter pylori (H. pylori) infection causes chronic inflammation which may play a pathogenic role in CSX. We surveyed the association of inflammation with H. pylori and its virulent strain (cytotoxin‐associated gene A positive; CagA+) infections with CSX. Material and Methods: Sixty patients with CSX (38 women/22 men; mean age: 51.8 ± 12.3) and 60 age‐ and gender‐matched healthy controls (39 women/21 men; mean age: 48.9 ± 6.3) were enrolled. Plasma samples were tested for the presence of IgG antibody to H. pylori using enzyme linked immunosorbent assay (ELISA) method. IgG‐ positive patients were determined by the presence of IgG antibody to CagA, also by ELISA method. Also, plasma levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α) were measured by ELISA method. Results: Patients with CSX were detected to have significantly higher plasma IL‐6 and TNF‐α level in comparison with normal controls (33.6 ± 3.5 vs 3.2 ± 0.4 and 24.2 ± 2.3 vs 3.1 ± 0.4, respectively; p < 0.01). The plasma levels of these inflammatory factors in CgA+ were significantly higher than those in CagA? (CSX: IL‐6: 43.05 ± 5.04 vs 23.97 ± 4.58 and TNF‐α: 31.43 ± 3.13 vs 16.47 ± 2.93, Controls: IL‐6: 3.52 ± 1.39 vs 2.90 ± 0.67 and TNF‐α: 5.39 ± 1.17 vs 2.22 ± 0.43, respectively; p < 0.05). Conclusion: The CagA+ strain of H. pylori, can not only be a trigger, and may also have a role via chronic inflammation in the pathogenesis of CSX.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

High Serum Leptin Is Associated with Attenuated Coronary Vasoreactivity

Objective: Hyperleptinemia, a hallmark of obesity, appears to be a risk factor for coronary artery disease. However, although leptin is a vasoactive hormone, no studies addressing leptin's effect on coronary perfusion have been performed. We examined the association between circulating leptin concentration and coronary vasoreactivity in young obese and nonobese males. Research Methods and Procedures: Myocardial blood flow was quantitated in 10 obese men (age 31 ± 7 years, BMI 34 ± 2 kg/m²) and 10 healthy matched nonobese men (age 33 ± 8 years, BMI 24 ± 2 kg/m²) using positron emission tomography and O‐15‐water. The measurements were performed basally and during adenosine infusion (140 μg/kg per minute). Results: Serum leptin was significantly higher in obese than nonobese subjects (10.3 ± 5.6 vs. 4.3 ± 2.5 ng/mL, p < 0.01). Basal myocardial blood flow was not significantly different between obese and nonobese subjects. Adenosine‐stimulated flow was blunted in obese (3.2 ± 0.6 mL/g per minute) when compared with nonobese subjects (4.0 ± 1.1 mL/g per minute, p < 0.05). Serum leptin concentration was inversely associated with adenosine‐stimulated flow in study subjects (r = ?0.50, p < 0.05). This association was no longer observed after adjustment for obesity and/or hyperinsulinemia. Discussion: Hyperleptinemia and reduced coronary vasoreactivity occur concomitantly in young obese but otherwise healthy men. Moreover, the adenosine‐stimulated myocardial flow is inversely related to prevailing concentration of serum leptin. Although this relationship appears to be explained by obesity and/or hyperinsulinemia, leptin might have a role in regulation of myocardial blood supply.     

Prostaglandin Endoperoxide H Synthase-2 (PGHS-2) Variants and Risk of Obesity and Microvascular Dysfunction Among Tunisians: Relevance of rs5277 (306G/C) and rs5275 (8473T/C) Genetic Markers

The purpose of this study was to determine the impact of six PGHS-2 genetic variants on obesity development and microvascular dysfunction. The study included 305 Tunisian subjects (186 normal weights, 35 overweights and 84 obeses). PCR analyses were used for allelic discrimination between polymorphisms. Prostaglandin (PGE2, PGI2), leptin, and matrix metalloproteinase (MMP1, 2, 3, 9) levels were evaluated by ELISA. Fatty acid composition was performed by gas chromatography–mass spectrometry. Our results revealed that subjects carrying the PGHS-2 306CC (rs5277) and 8473CC (rs5275) genotypes present higher anthropometric values compared to wild-type genotypes (306GG, BMI (Kg/m²): 27.11?±?0.58; WC (cm): 93.09?±?1.58; 306CC, BMI: 33.83?±?2.46; WC: 109.93?±?5.41; 8473TT, BMI: 27.75?±?0.68; WC: 93.96?±?1.75; 8473CC, BMI: 33.72?±?2.2; WC: 117.89?±?2.94). A reduced microvascular reactivity and a higher PGE2 level were also found in individuals with the 306CC and 8473CC genotypes in comparison to 306GG and 8473TT carriers (306GG, Peak Ach-CVC (PU/mmHg): 0.46?±?0.03; PGE2 (pg/ml): 7933.1?±?702; 306CC, Peak Ach-CVC: 0.24?±?0.01; PGE2: 13,380.3?±?966.2; 8473TT, Peak Ach-CVC: 0.48?±?0.05; PGE2: 7086.41?±?700.31; 8473CC, Peak Ach-CVC: 0.23?±?0.01; PGE2: 13,175.7?±?1165.8). Fatty acid analysis showed a significant increase of palmitic acid (PA) (34.2?±?2.09 vs. 16.82%?±?1.76, P?<?0.001), stearic acid (SA) (25.76?±?3.29 vs. 9.05%?±?2.53, P?<?0.001), and linoleic acid (LA) (5.25?±?1.18 vs. 0.5%?±?0.09, P?<?0.001) levels in individuals carrying the PGHS-2 306CC genotype when compared to GG genotype individuals. Subjects with the 8473CC genotype showed also a significant increase of PA, SA ,and LA levels when compared to TT genotype carriers (PA: 38.02?±?1.51 vs. 12.65%?±?1.54, P?<?0.001; SA: 32.96?±?1.87 vs. 1.38%?±?0.56, P?<?0.001; LA: 26.84?±?2.09 vs. 3.7%?±?1.54, P?<?0.001). Logistic regression analysis revealed that PGHS-2 306CC and 8473CC variants are significantly associated with obesity status (OR 6.25, CI (1.8–21.6), P?=?0.004; OR 3.01, CI (1.13–8.52), P?=?0.03, respectively). Haplotypes containing the C₃₀₆:T₈₄₇₃ (OR 2.91; P?=?0.01) and G_306:C₈₄₇₃ (OR 5.25; P?=?0.002) combinations were associated with an enhanced risk for obesity development in the studied population. In conclusion, our results highlight that PGHS-2 306G/C and 8473T/C variants could be useful indicators of obesity development, inflammation, and microvascular dysfunction among Tunisians.

     

Metformin restores the correlation between serum-oxidized LDL and leptin levels in type 2 diabetic patients

Abstract

Introduction

Leptin has lipid peroxidation properties in healthy individuals. Here we aimed to study the correlation between serum-oxidized low-density lipoprotein (ox-LDL) and leptin levels in patients with type 2 diabetes. We also studied the effect of metformin therapy on the correlation between serum ox-LDL and leptin levels in patients with newly diagnosed diabetes.

Methods

We performed a cross-sectional study on two groups of patients with type 2 diabetes stratified according to (1) patients with newly diagnosed diabetes and (2) patients with long-standing diabetes plus healthy controls. Patients with newly diagnosed diabetes were followed for 3 months after the initiation of metformin therapy.

Results

Patients with type 2 diabetes had a higher serum ox-LDL, ox-LDL/LDL ratio, waist circumference, fasting blood sugars (FBSs), hemoglobin A1C (HbA1C), triglyceride, homeostatic model assessment of insulin resistance (HOMA-IR) and a lower serum leptin levels than controls. Serum ox-LDL, ox-LDL/LDL ratio (0.08 (0.08–0.12) vs. 0.06 (0.05–0.08), P < 0.001) and HOMA-IR (3.26 ± 0.23 vs. 2.93 ± 0.32; P < 0.01) were decreased when serum leptin levels (15.9 ± 1.6 vs. 21.4 ± 2.5, P < 0.01) were increased after 3 months of metformin therapy. This remained significant after multiple adjustments for age, body mass index, FBS, HbA1c, and HOMA-IR. Leptin was significantly correlated with ox-LDL/LDL ratio in controls (r = 0.78, P < 0.01), and in patients with newly diagnosed diabetes (r = 0.4, P < 0.05), after metformin therapy. There were not any correlation between leptin and ox-LDL/LDL ratio in patients with long-standing diabetes and patients with newly diagnosed diabetes before treatment.

Discussion

Metformin restores the positive correlation between serum ox-LDL and leptin levels in patients with type 2 diabetes.     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.     

Biomarker-specific differences between transpulmonary and peripheral arterial–venous blood sampling in patients with pulmonary hypertension

Abstract

Purpose: Transpulmonary biomarkers may provide insight into pulmonary hypertension (PH) pathophysiology, but require cardiac catheterization. We investigated whether the peripheral arterial–venous ratio (PR) could substitute for the transpulmonary ratio (TPR).

Materials and methods: Blood from the pulmonary artery (PA), pulmonary arterial wedge (PAW), peripheral venous, and peripheral arterial positions was analysed for ET-1, NT-pro-BNP and cAMP levels in subjects with no PH (n?=?18) and PH due to left heart disease (PH-LHD), which included combined pre- and post-capillary PH (Cpc-PH; n?=?7) and isolated post-capillary PH (Ipc-PH; n?=?9). Bland–Altman comparisons were made between peripheral venous and PA samples and between peripheral arterial and PAW samples. TPR was defined as [PAW]/[PA].

Results: For ET-1, Bland–Altman analysis indicated negative bias (?24%) in peripheral arterial compared to PAW concentration and positive bias (23%) in peripheral venous compared to PA concentration. There was <10% absolute bias for NT-pro-BNP and cAMP. For ET-1, there was no difference in PR between Cpc-PH and Ipc-PH (0.87?±?0.4 vs. 0.94?±?0.6, p?=?0.8), whereas there was a difference in TPR (2.2?±?1.1 vs. 1.1?±?0.2, p?<?0.05).

Conclusions: In PH-LHD, peripheral samples may be inadequate surrogates for transpulmonary samples, particularly when measuring mediators with prominent pulmonary secretion or clearance, such as ET-1.     

Correlation between circulatory Kisspeptin and Adipokines in normal and over-weight Saudi females during menstrual cycle

We analyzed the association between kisspeptin and plasma adipokines (leptin and adiponectin) in normal-weight and over-weight young females. Thirty young Saudi females, based on their body mass index (BMI), were divided into two groups (15 students/group) as (1) Normal weight (NW): BMI = 18.5–24.99 and (2) Over-weight/obese (OW): BMI ≥ 25. Serum adipokines (leptin, adiponectin) and kisspeptin levels were measured in early follicular, pre-ovulatory, and luteal phase in both groups with ELISA. Menstrual cycle phases were confirmed by serum estradiol levels. There was no association of kisspeptin with leptin in early follicular (r ?0.34, P 0.31), pre-ovulatory (r ?0.32, P 0.34) and luteal phase (r 0.21, P 0.54). Likewise, kisspeptin was not found to be correlated with adiponectin in early follicular (r 0.41, P 0.21), pre ovulatory (r 0.24, P 0.48), and luteal phase (r 0.40, P 0.23) when values recorded during different time points during the cycle were plotted with each other.     

A comparison of native and non-urate Total Antioxidant Capacity of fasting plasma and saliva among middle-aged and older subjects

Objectives: As plasma and salivary total antioxidant capacity (TAC) is mainly contributed by uric acid (UA), the present study measures non-urate TAC (Nu-TAC). The aim of the study was to correlate plasma native TAC, Nu-TAC and UA with their salivary analogues, and compare the UA contribution in both body fluids using two different methods.

Methods: The study involved 55 middle-aged and older subjects (66.7?±?4.5 years). TAC was determined simultaneously with two methods (ferric reducing ability of plasma – FRAP, 2.2-diphenyl-1-picryl-hydrazyl – DPPH and countertypes for saliva – FRAS and DPPHS test), with and without UA (native TAC and Nu-TAC, respectively). Plasma UA and salivary UA (SUA) were assessed.

Results: Subjects with increased FRAP, DPPH and UA had higher FRAS, DPPHS and SUA, respectively (P?P?Discussion: Our findings suggest that saliva is a good predictor for native plasma TAC but not for Nu-TAC. UA level is comparably dominant in saliva and in plasma according to DPPH, but lower in plasma according to FRAP.     

Hyperadiponectinemia in Newborns: Relationship with Leptin Levels and Birth Weight

Objective: Adiponectin is the only adipose‐specific hormone that, despite its exclusive production by adipose tissue, is reduced in obesity and is inversely correlated with leptin levels in adults. The aim of this study was to evaluate the adiponectin concentration in umbilical cord blood at different gestational ages and to investigate its possible associations with leptin levels and birth weight. Research Methods and Procedures: Umbilical cord blood was obtained from 132 newborns (male = 65, female = 67, gestational age: 35 to 42 weeks). The anthropometric variables of the newborns studied were birth weight, birth length, body weight/body length, and ponderal index. Adiponectin, insulin, and leptin levels were measured by radioimmunoassay methods. Results: Adiponectin levels in males were not different from those in females (24.10 ± 0.81 vs. 25.62 ± 0.84 μg/mL, p = 0.280). Adiponectin concentrations were positively correlated with birth weight (p < 0.05), birth length (p < 0.05), body weight/body length (p < 0.05), gestational age (p < 0.01), and leptin levels (p < 0.01). Discussion: These findings indicate that adiponectin is present in umbilical cord blood after 35 to 42 weeks of gestation, with higher levels than those usually found in adults, no gender differences, and a positive correlation with birth weight and leptin. These results suggest that not only could neonatal hyperadiponectinemia be associated with the increase of adiponectin production by fetal adipose tissue but also with a possible reduction in an unknown mechanism related to the suppression of adiponectin observed in adults.     

Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis

Objective: Noninvasive diagnostics of early stages of coronary artery disease and discrimination between various extents of vascular lesions in patients is an important clinical problem especially considering wide spread use of cholesterol lowering drugs that affect lipid and lipoprotein profiling. The main goal of our study was to evaluate applicability of new combinations of noninvasive biomarkers such as leptin to insulin and adiponectin to endothelin ratios, for detection of early stages of coronary atherosclerosis versus later stages of the disease.

Patients and methods: A number of previously validated serum biomarkers were tested in a group of 500 patients with coronary artery disease and examined for their association with severity of coronary lesion according to Gensini score determined by coronary angiography.

Results: Lowest extent of coronary lesions was associated with significant increase in apoA-I levels and with significantly increased ratios of adiponectin to endothelin and leptin to insulin. In male but not in female patients, adiponectin to endothelin ratio below 7.0 was associated with Gensini score representing early to high coronary lesions (p?=?0.02). In female but not in male patients, leptin to insulin ratio below 3.5 was associated with Gensini score representing early to high coronary lesions (p?=?0.013).

Conclusion: Leptin to insulin and adiponectin to endothelin ratios are novel derived biomarkers useful for noninvasive diagnostics of initial stages of coronary lesions in patients with coronary artery disease.     

Weight Loss Increases Soluble Leptin Receptor Levels and the Soluble Receptor Bound Fraction of Leptin

Objective: Soluble leptin receptor (sOB‐R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound/free ratio after pronounced weight reduction. Research Methods and Procedures: A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass, leptin, and sOB‐R concentrations before and 1 year after Swedish adjustable gastric banding. Results: Anthropomorphic measures displayed a significant reduction of body mass index [(42.9 ± 5.6 to 32.9 ± 6.0 kg/m² (mean ± SD)]. Fat mass decreased from 56.3 ± 9.0 to 33.9 ± 12.5 kg. Plasma leptin concentration decreased from 44.6 ± 18.0 to 20.0 ± 13.1 ng/mL (p < 0.001), whereas the sOB‐R levels increased from 11.1 ± 3.6 to 16.6 ± 6.0 U/mL after weight‐reducing surgery. Thus, the sOB‐R bound fraction of leptin increased from 7% to 33%. Discussion: This work demonstrates a relationship between weight loss, leptin, and sOB‐R concentrations in vivo. During weight loss, leptin levels decreased, whereas sOB‐R levels and the receptor bound fraction of leptin increased. Thus, sOB‐R may negatively regulate free leptin.     

Myeloperoxidase expression in human colonic mucosa is related to systemic oxidative balance in healthy subjects

Objectives: To improve understanding of the preclinical stage of colonic inflammation by exploring the existence of a link between early inflammatory changes in the colonic mucosa and the systemic redox balance.

Methods: Clinical characteristics, a fasting blood draw, and mucosal biopsies from the right, left, and sigmoid-rectum colonic tracts collected from 28 healthy individuals (14/14 males/females) who underwent colonoscopy. Myeloperoxidase (MPO) positive cells infiltrating colonic mucosa specimens were assessed by immunohistochemistry, and patients divided into high or low MPO expressing cells/optical field groups (MPO^high or MPO^low, respectively).The systemic oxidative balance has been studied through derived-Reactive Oxygen Metabolites (d-ROMs), Biological Antioxidant Potential (BAP), and Lipoperoxide-cholesterol Oxidizing (LP-CHOLOX) tests on serum.

Results: MPO^high patients demonstrated an increased systemic oxidative stress compared to MPO^low individuals (P?=?0.035), especially when MPO is referred to the left-sided colonic mucosa (P?=?0.007). MPO^low subjects in the sigmoid-rectum showed a significant higher antioxidant capacity in the serum (P?P?=?0.044), and a decreasing gradient in MPO expression moving from the cecum to the rectum (ascendant, descendant, and sigmoid-rectum: 3.7?±?2.8, 3.1?±?1.7, and 1.4?±?0.5, respectively, P?=?0.012) were also found and discussed.

Discussion: The study is the first demonstrating a connection between systemic redox balance and MPO expression in the colonic mucosa, according to the colonic tract and patient gender. Further research evaluating the MPO expression in the human colon and its relationship with pathological conditions could benefit from these results.     

Serum RBP4 positively correlates with triglyceride level but not with BMI,fat mass and insulin resistance in healthy obese and non-obese individuals

Abstract

Purpose: Retinol binding protein 4 (RBP4) has recently been identified as an adipokine possibly involved in the development of impaired glucose metabolism. We aimed to test serum RBP4 in healthy non-obese individuals and in patients with well-characterized phenotype: obesity without confounding effects of diabetes, metabolic syndrome or dyslipidaemia. Additionally, we examined whether serum RBP4 is associated with anthropometric parameters, insulin resistance and blood lipid parameters.

Patients and methods: Twenty-eight patients with obesity and no co-morbidities and twenty-five age-matched lean controls were recruited. Anthropometric parameters, body composition, fasting blood lipid profile, RBP4, glucose and insulin were assessed and HOMA-IR was calculated.

Results: Mean concentration of RBP4 did not differ between studied groups (in obese patients was 33.93?±?4.46?µg/ml and 32.53?±?2.53?µg/ml in non-obese controls). RBP4 positively correlated with serum triglycerides in obese and non-obese individuals (r?=?0.74, p?=?0.03 and r?=?0.62, p?=?0.02, respectively) and did not show any significant associations with HOMA-IR, anthropometric and body composition parameters.

Conclusions: Excessive adiposity without co-morbidities is not associated with higher levels of circulating RBP4. Serum RBP4 cannot be considered as a direct predictive marker for impaired glucose metabolism. RBP4 possibly contributes to lipid metabolism.     

Ghrelin Does Not Influence Gastric Emptying in Obese Subjects

Objective: To evaluate the relationship between fasting plasma concentrations of ghrelin and gastric emptying in obese individuals compared with lean subjects. Research Methods and Procedures: We included 20 obese patients (9 men and 11 women, BMI > 30 kg/m²) and 16 nonobese control subjects (7 men and 9 women, BMI ≤ 25 kg/m²). Gastric emptying of solids (egg sandwich labeled with radionuclide) was measured at 120 minutes with (99m)Tc‐single photon emission computed tomography imaging. Ghrelin and leptin were analyzed by radioimmunoassay and ELISA methods, respectively. Results: The gastric half‐emptying time was similar in obese men and women (67.8 ± 14.79 vs. 66.6 ± 13.56 minutes) but significantly shorter (p < 0.001) than in the control population (men: 88.09 ± 11.72 minutes; women: 97.25 ± 10.31 minutes). Ghrelin levels were significantly lower in obese subjects (131.37 ± 47.67 vs. 306.3 ± 45.52 pg/mL; p < 0.0001 in men and 162.13 ± 32.95 vs. 272.8 ± 47.77 pg/mL; p < 0.0001 in women). A negative correlation between gastric emptying and fasting ghrelin levels was observed only in lean subjects (y = ?0.2391x + 157.9; R² = 0.95). Also, in the lean group, ghrelin was the only significant independent determinant of gastric emptying, explaining 98% of the variance (adjusted R²) in a multiple regression analysis. Discussion: This report shows that, in humans, gastric emptying is faster in obese subjects than in lean controls and that, whereas ghrelin is the best determinant of gastric kinetics in healthy controls, this action is lost in obesity.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.