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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is associated with increased bile stasis and cholesterol saturation, and an increased risk of gallstone development. Conversely, bile composition is normalized following reduction in body weight. It would appear advantageous to promote weight loss in obesity, which would reduce the predisposition to gallstone formation. Despite the potential health benefits of weight reduction, very-low-calorie diets appear to increase the risk for cholesterol crystal and gallstone formation. The incidence of gallstone formation seems to be dependent on the degree of caloric restriction, the rate of weight loss, and the duration of the dietary intervention. Thus, faster rates of weight loss for longer periods of time are associated with increased risk. Available data obtained from prospective studies of subjects during active weight loss suggest that newly formed gallstones occur within 4 weeks and with incidence rates 15 to 25-fold higher than in the general obese population. The stones produce symptoms in approximately one-third of the subjects, of whom approximately one-half will undergo surgery. Proposed mechanisms underlying gallstone formation during weight reduction include bile stasis due to reduced caloric intake, increased biliary cholesterol saturation secondary to increased cholesterol mobilization, and increased nucleation due to changes in bile arachidonate and glycoprotein concentrations. Data are lacking on the effects of gradual rates of weight loss and risk of gallstone formation.
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PMID:Gallstone formation and weight loss. 1635 May 61

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.
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PMID:Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells? 1658 11

Whereas antiphospholipid antibodies (aPL) are associated with thrombotic events and recurrent spontaneous abortion (RSA), the contribution of anti-beta2 glycoprotein 1 (beta2GP1) and anti-annexin V antibodies as risk factors for RSA remain poorly understood. We investigated anti-beta2-GPI and anti-annexin V IgM and IgG antibodies as potential risk factors for RSA in 200 women with more than three consecutive idiopathic RSA, and 200 age-matched, healthy, parous women. Pearson's chi squared test analysis showed that while anti-beta2-GPI IgG (P = 0.416) and IgM (P = 0.72) were comparable between patients and controls, elevated anti-annexin V IgG (P = 0.006), but not IgM (P = 0.084), was more pronounced in patients. Higher frequencies of elevated IgG-only (P = 0.005), but not IgM-only (P = 1.000; OR = 6.66), anti-annexin V antibodies were noted among patients. Multinomial regression analysis showed that body-mass index (overweight and obesity; P = 0.008), education status (P < 0.001) and anti-beta2-GPI IgM (P = 0.033), but not IgG (P = 0.723), were associated with early abortion, while anti-beta2-GPI IgG (P = 0.030) and anti-annexin V IgG (P = 0.004) were associated with late RSA. For combined early-late RSA, the only variable selected was education status (P < 0.001), and neither anti-annexin V nor anti-beta2-GPI IgM and IgG was associated with early-late RSA. Accordingly, anti-annexin V and anti-beta2-GPI should be regarded as independent risk markers of RSA.
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PMID:A case-control study on the association of idiopathic recurrent pregnancy loss with autoantibodies against beta2-glycoprotein I and annexin V. 1659 32

Hypogonadotrophic hypogonadism (HH) is characterized by delayed or absent pubertal development secondary to gonadotrophin deficiency. HH can result from mutations of the gonadotrophin-releasing hormone receptor 1, the gonadotrophin beta-subunits, or various transcription factors involved in pituitary gland development. HH occurs in DAX1 mutations when associated with adrenal insufficiency (adrenal hypoplasia congenita), and is also linked with obesity in patients with mutations of leptin and its receptor, as well as mutations in prohormone convertase 1. Rarely, HH has resulted from kisspeptin receptor (GPR54) mutations, a gene implicated in the regulation of pubertal onset. When occurring with anosmia (a lack of sense of smell), HH is referred to as Kallmann's syndrome (KS). Two KS-related loci are currently known: KAL1, encoding anosmin-1, responsible for X-linked KS, and KAL2, encoding the fibroblast growth factor receptor 1 (FGFR1), mutated in autosomal dominant KS. Anosmin-1 is an extracellular glycoprotein with some unique structural characteristics; it interacts with both urokinase-type plasminogen activator and FGFR1. It has previously been shown that anosmin-1 enhances FGFR1 signalling in a heparan sulphate-dependent manner, and proposed that anosmin-1 fine-tunes FGFR1 signalling during olfactory and GnRH neuronal development. Here, we review the known normosmic causes of HH, and discuss novel developmental and molecular mechanisms underlying KS; finally, we introduce three novel genes (NELF, PKR2, and CHD7) that may be associated with some phenotypic features of KS.
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PMID:Molecular pathogenesis of Kallmann's syndrome. 1719 Oct 30

Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.
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PMID:Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome. 1826 32

Sibutramine hydrochloride monohydrate, chemically 1-(4-chlorophenyl)-N,N-dimethyl-alpha-(2-methylpropyl) hydrochloride monohydrate (SB.HCI.H20), was approved by the U.S. Food and Drug Administration for the treatment of obesity. The objective of this study was to develop, validate, and compare methods using UV-derivative spectrophotometry (UVDS) and reversed-phase high-performance liquid chromatography (HPLC) for the determination of SB.HCI.H20 in pharmaceutical drug products. The UVDS and HPLC methods were found to be rapid, precise, and accurate. Statistically, there was no significant difference between the proposed UVDS and HPLC methods. The enantiomeric separation of SB was obtained on an alpha-1-acid glycoprotein column. The R- and S-sibutramine were eluted in < 5 min with baseline separation of the chromatographic peaks (alpha = 1.9 and resolution = 1.9).
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PMID:Development and validation of sensitive methods for determination of sibutramine hydrochloride monohydrate and direct enantiomeric separation on a protein-based chiral stationary phase. 1856 3

Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight component of the fibrillin-rich microfibril. Gene-targeted inactivation of MAGP-1 reveals a complex phenotype that includes increased body weight and size due to excess body fat, an altered wound healing response in bone and skin, and a bleeding diathesis. Elastic tissues rich in MAGP-1-containing microfibrils develop normally and show normal function. The penetrance of MAGP-1-null phenotypes is highly variable and mouse strain-dependent, suggesting the influence of modifier genes. MAGP-1 was found to bind active transforming growth factor-beta (TGF-beta) and BMP-7 with high affinity, suggesting that it may be an important modulator of microfibril-mediated growth factor signaling. Many of the phenotypic traits observed in MAGP-1-deficient mice are consistent with loss of TGF-beta function and are generally opposite those associated with mutations in fibrillin-1 that result in enhanced TGF-beta signaling. Increased body size and fat deposition in MAGP-1-mutant animals are particularly intriguing given the localization of obesity traits in humans to the region on chromosome 1 containing the MAGP-1 gene.
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PMID:Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes in multiple organ systems. 1862 13

The main goal of this study was to compare the expression of Zinc-alpha2-glycoprotein (ZAG), a recently described adipokine, in obese and lean subjects. ZAG expression was determined by Real-time PCR analysis in subcutaneous abdominal adipose tissue of eighteen young men, 9 lean (BMI = 23.1 +/- 0.4 kg/m2) and 9 obese (34.7 +/- 1.2 kg/m2) with a similar habitual dietary intake of fat and physical activity, which were assessed by validated methods. Our data revealed that ZAG gene was downregulated (-70%; p < 0.05) in subcutaneous adipose tissue of obese compared to lean subjects. Moreover, statistically significant positive correlations between ZAG gene expression and serum adiponectin (r = 0.89; p < 0.01) and a negative correlation with the plasma levels of leptin (r = -0.82; p < 0.05) and waist circumference (r = -0.64; p < 0.05) were found in obese subjects. Our data suggest that this novel adipokine could play a role in human susceptibility to obesity related disorders and that upregulation of ZAG could be a promising therapeutic target for metabolic syndrome treatment.
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PMID:ZAG, a lipid mobilizing adipokine, is downregulated in human obesity. 1866 96

Roux-en-Y gastric bypass surgery (RYGBP) leads to improvements in satiety and obesity-related comorbidities. The mechanism(s) underlying these improvements are not known but may be revealed in part by discovery proteomics. Therefore, fasting plasma was collected from 12 subjects (mean BMI >45) during RYGBP and during a second procedure approximately 17 months later. Body weight, obesity-related comorbidities, and medication use were decreased after RYGBP. Mass spectrometry-based proteomic analysis was performed on a subset of seven samples using isobaric isotope-coded affinity tags (four plex iTRAQ). Initial proteomic analysis (n = 7) quantified and identified hundreds of plasma proteins. Manual inspection of the data revealed a 2.6 +/- 0.5-fold increase in apolipoprotein A-IV (apo A-IV, gene designation: APOA4), a approximately 46-kDa glycoprotein synthesized mainly in the bypassed small bowel and liver after RYGBP. The change in apo A-IV was significantly greater than other apolipoproteins. Immunoblot analysis of the full longitudinal sample set (n = 12) indicated even higher increases (8.3 +/- 0.2 fold) in apo A-IV. Thus iTRAQ may underestimate the changes in protein concentrations compared to western blotting of apo A-IV. Apo A-IV inhibits gastric emptying and serves as a satiety factor whose synthesis and secretion are increased by the ingestion of dietary fat. It also possesses anti-inflammatory and antiatherogenic properties. Based on these functions, we speculate changes in apo A-IV may contribute to weight loss as well as the improvements in inflammation and cardiovascular disease after RYGBP. In addition, the findings provide evidence validating the use of iTRAQ proteomics in discovery-based studies of post-RYGBP improvements in obesity-related medical comorbidities.
Obesity (Silver Spring) 2009 Jan
PMID:Apolipoprotein A-IV, a putative satiety/antiatherogenic factor, rises after gastric bypass. 1894 73

Obesity can be considered as a low grade inflammatory disease, characterized by increased plasma levels of proinflammatory cytokines such as tumoral necrosis factor-a (TNF-a), and acute phase reactant proteins like C-reactive protein. In this context, some cytokines of the interleukin-6 (IL-6) family have been involved in the inflammatory processes associated to obesity. In addition to IL-6, the IL-6 cytokine family includes IL-11, ciliary neurotrophic factor (cntf), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF) y Oncostatin M (OsM). These proteins are also known as gp130 cytokines because all of them exert their action via the glycoprotein 130 (gp130) as a common transducer protein within their functional receptor complexes. However, their role in obesity and related disorders is controversial; thus, whereas some studies have described the involvement of gp130 cytokines in the development of obesity and its related cluster of pathophysiologic conditions like insulin-resistance, fatty liver and cardiovascular diseases, other trials have proposed the gp130 receptor ligands as therapeutic targets in the treatment of obesity and its related disorders. In fact, CNTF treatment has demonstrated to be effective in the reduction of body weight, by promoting the inhibition of food intake and the activation of the energy expenditure, together with an improvement of insulin sensitivity. This review analyzes the potential therapeutic role of some of the gp130 ligands in obesity and related diseases.
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PMID:[Obesity, inflammation and insulin resistance: role of gp 130 receptor ligands]. 1895 60


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