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

The prevalence of Type 2 diabetes is increasing dramatically as a result of the obesity epidemic, and poses a major health and socio-economic burden. Type 2 diabetes develops in individuals who fail to compensate for insulin resistance by increasing pancreatic insulin secretion. This insulin deficiency results from pancreatic beta-cell dysfunction and death. Western diets rich in saturated fats cause obesity and insulin resistance, and increase levels of circulating NEFAs [non-esterified ('free') fatty acids]. In addition, they contribute to beta-cell failure in genetically predisposed individuals. NEFAs cause beta-cell apoptosis and may thus contribute to progressive beta-cell loss in Type 2 diabetes. The molecular pathways and regulators involved in NEFA-mediated beta-cell dysfunction and apoptosis are beginning to be understood. We have identified ER (endoplasmic reticulum) stress as one of the molecular mechanisms implicated in NEFA-induced beta-cell apoptosis. ER stress was also proposed as a mechanism linking high-fat-diet-induced obesity with insulin resistance. This cellular stress response may thus be a common molecular pathway for the two main causes of Type 2 diabetes, namely insulin resistance and beta-cell loss. A better understanding of the molecular mechanisms contributing to pancreatic beta-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes.
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PMID:Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes. 1848 55

Endocannabinoids act through the cannabinoid receptor 1 (CB1) and has both orexigenic and peripheral metabolic effects. It is not yet fully understood whether all the beneficial effects on the metabolic profile by CB1 antagonism are induced by the weight loss or also by direct peripheral effects. The present study was intended to further elucidate this question and to investigate whether tolerance development to the hypophagic effect could be attenuated by cyclic treatment. We performed an intervention study in 40 lean rats over 4 weeks. The rats were divided in four groups: a control group, two groups treated with the CB1 antagonist Rimonabant either continuously or cyclically, and one group pair fed with the continuous Rimonabant group to obtain the same body weight. During the first 6 days, food intake was less in the continuous Rimonabant group compared to the control group (P < 0.01). Throughout the study period, the cyclic Rimonabant group had a smaller food intake than the continuous Rimonabant group (P < 0.05). After 4 weeks, the cyclic Rimonabant group had a reduced weight gain compared to the control group (P < 0.05). Serum levels of glycerol and free fatty acids (nonesterified fatty acid, NEFA) were significantly reduced in both treated groups compared to the untreated groups, and levels of triglycerides showed the same tendency. Cyclic treatment with Rimonabant is able to inhibit tolerance development on food intake, which resulted in reduction in body weight. Rimonabant treatment is associated with reduced serum levels of glycerol, NEFA, and triglyceride which seem independent of body weight changes.
Obesity (Silver Spring) 2008 Nov
PMID:Effects on food intake and blood lipids of cannabinoid receptor 1 antagonist treatment in lean rats. 1871 71

Human mitochondria can be studied either in biopsies or by measuring flux through ATP synthase and phosphocreatine recovery using magnetic resonance spectroscopy. Myocellular ATP production (flux through ATP synthase [fATP]) increases by up to 90% during 8 h of insulin stimulation. Fasting mitochondrial function is 14-40% lower than in controls in the presence of insulin resistance, as seen in those with type 2 diabetes, their insulin-resistant relatives or the obese. Insulin-stimulated fATP is abolished in insulin-resistant relatives and patients with type 2 diabetes, and patients frequently show decreased mitochondrial size/density. Age, fat mass, physical activity, plasma NEFA and glucose all correlate negatively with mitochondrial function, but it is for methodological reasons difficult to determine whether reduced mitochondrial content or function account for reduced ATP production in insulin resistance. Experimental plasma NEFA elevation appears to inhibit mitochondrial function by interfering with the metabolic actions of insulin, which might explain impaired mitochondrial function in obesity. Alternatively, primary mitochondrial abnormalities, as seen in those with inherited risk of type 2 diabetes, could decrease lipid oxidation, thereby raising circulating and intracellular NEFA levels. In type 2 diabetes, chronic hyperglycaemia and dyslipidaemia could first diminish the function, and subsequently reduce the size or density of mitochondria via oxidative stress and apoptosis. Many questions remain unsolved, including (1) which mechanisms regulate mitochondrial adaptation to nutrient overload; (2) what factors control the expression of genes encoding mitochondrial proteins and other signals involved in mitochondrial biogenesis; (3) which geno/phenotypes are associated with both insulin resistance and mitochondrial abnormalities; and (4) which are the most promising targets for improving mitochondrial fitness in insulin resistance?
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PMID:Mitochondrial fitness and insulin sensitivity in humans. 1880 78

Conjugated linoleic acid (CLA) has anti-obesity effects, but induces fatty liver in mice. The present study investigated whether co-administration of arachidonic acid (ARA) attenuates fat accumulation in the mouse liver induced by CLA. Male mice (8 weeks old) were given diets with either no addition of dietary fat (control), 3 % linoleic acid (LA), 3 % CLA, 3 % CLA+1 % ARA, or 3 % CLA+2 % ARA for 4 weeks. The perirenal fat weight in ARA-treated groups decreased similarly as with CLA alone, when compared to control or LA. Plasma TAG concentration was significantly higher in the CLA group than in either CLA+ARA group, while plasma cholesterol and NEFA concentrations did not vary among the groups. In contrast to visceral fat, liver weight was significantly higher in the CLA group than in the control or LA groups, and the effects of CLA were attenuated by ARA. TAG and cholesterol were markedly accumulated in the liver with dietary CLA, whereas co-administration with ARA, at either concentration, suppressed CLA-induced lipid accumulation. Liver PGE(2) was enhanced by a combination of CLA and ARA when compared with CLA alone, but PGE(1) level was not significantly different among groups. In conclusion, fatty liver induced by CLA was attenuated by co-administration with ARA, furthermore, a combination of these fatty acids maintained the anti-obese effect of CLA.
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PMID:Arachidonic acid prevents fatty liver induced by conjugated linoleic acid in mice. 1894 40

Conjugated linoleic acid isomers may affect the onset and severity of several diseases, including tumors, atherogenesis, and obesity. They may also modulate the immune response. However, little information regarding the most advantageous duration of CLA supplementation is available. The purpose of this study was to determine whether the length of dietary CLA supplementation of a sow affects growth, immune components, and metabolic and hormonal factors in lactating sows and piglets. Gestating sows were fed a control (0%) and a 0.5% CLA-supplemented diet beginning 7 d before parturition and ending 7 d postpartum (T1), or until weaning (T2; 7 sows per treatment). Colostrum and sow and piglet blood samples were collected for the determination of serum metabolite concentrations and immunoglobulin titer. Piglet BW at weaning were greater (P < 0.05) in the CLA groups compared with the control. Dietary CLA supplementation increased (P < 0.05) serum thyroxine concentration in sows, but serum insulin, glucose, NEFA, IGF-I, and leptin concentrations were not affected by CLA supplementation. Colostral IgG, IgA, and IgM titers were greater in sows fed CLA than in control sows (P < 0.05). At weaning (21 d), serum IgG titer of the piglets was greater (P < 0.05) in the T1 and T2 groups than the control group, but at 13 d postweaning, a difference (P < 0.05) was observed between the control and T2 group. The results from this study indicate potential beneficial effects of 0.5% dietary CLA supplementation from 7 d before parturition until 7 d postpartum in improving BW at weaning and immune components in piglets.
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PMID:Effect of dietary conjugated linoleic acid supplementation in sows on performance and immunoglobulin concentration in piglets. 1928 21

The present study is designed to investigate how and to what extent sympathovagal behavior in a balanced low-calorie diet relates to favorable changes of body mass, waist circumference, and/or metabolic risk factors. The study involved 28 mildly obese women without clinical complications, who underwent an 8-week calorie restriction program using a 1,200-kcal daily diet with an adequate nutrient content; including two regular meals, and one formula meal replacement. All subjects were examined before and after the dietary intervention. We measured anthropometric parameters, blood pressure, and biochemical blood profiles for lipid metabolism. Autonomic nervous system activity was evaluated by heart rate variability power spectral analysis. The dietary intervention induced moderate, but significant reduction of waist circumference (-5.3% +/- 0.8%), body fat percentage (-5.8% +/- 0.8%), and body mass (-6.6% +/- 0.5%). Linear regression analysis showed that Deltavery low frequency (VLF) power reflecting energy metabolic- and thermoregulatory sympathetic function significantly correlated to Deltawaist circumference (r = -0.53, P < 0.01), Deltabody fat percentage (r = -0.39, P < 0.05), Deltabody mass (r = -0.43, P < 0.05), DeltaHDL-cholesterol/total cholesterol ratio (HDL-C/TC) (r = 0.62, P < 0.001), and Deltanonesterified fatty acids (NEFA) (r = 0.56, P < 0.01). A stepwise multiple regression analysis additionally revealed that Deltawaist circumference (P = 0.024), DeltaHDL-C/TC (P = 0.013), and DeltaNEFA (P = 0.016) were significant and independent factors, which contributing to the variance in DeltaVLF power (r(2) = 0.61). Although causes and consequences of obesity continue to elude researchers, the present study indicates that thermoregulatory sympathetic activity relates to moderate waist-circumference reduction together with favorable changes of blood lipid profiles after short-term dietary modification in mildly obese women.
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PMID:Thermoregulatory sympathetic nervous system activity and diet-induced waist-circumference reduction in obese Japanese women. 1938 59

Nesfatin/nucleobindin 2 (NUCB2) is expressed in the appetite-control hypothalamic nuclei and brainstem nuclei. Nesfatin/NUCB2 expression in the paraventricular nucleus of the hypothalamus was modulated by starvation and refeeding. Intracerebroventricular administration of nesfatin-1 dose-dependently inhibited food intake for 6 hours in male Wistar and leptin resistant, Zucker fatty rats. Intraperitoneal administration of nesfatin-1 and its mid-segment (M30) dosedependentlyinhibited food intake for 3 hours in male ICR mice. Intraperitoneal administration of M30 also decreased foodintake in leptin-resistant, genetically obese (ob/ob), diabetic (db/db) mice and mice fed a 45% high fat diet for 28 days. Intraperitoneal administration of M30 increased proopiomelanocortin and cocaine- and amphetamine- related peptide mRNA expression in the nucleus of the solitary tract of mice. In addition, intranasal administration of nesfatin-1 significantly inhibited food intake for 6 hours in male Wistar rats. We summarize recent observations about nesfatin-1, and attempt to present future direction of nesfatin-1 research for developing a new anti-obesity treatment.
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PMID:Nesfatin-1: an overview and future clinical application. 1946 Nov 59

Propionyl-L-carnitine (PLC) is an SCFA esterified to carnitine that plays an important role in fatty acid oxidation and energy expenditure, in addition to having a protective effect on the endothelium. In order to evaluate the effect of PLC on an animal model of obesity, insulin resistance and, consequently, endothelial dysfunction, lean and obese Zucker rats (OZR) received either vehicle- or PLC-supplemented drinking water (200 mg/kg per d) for 20 weeks. Body weight, food intake, systolic blood pressure and heart rate were controlled weekly and an oral glucose tolerance test was performed. Fasting glucose, TAG, cholesterol, HDL, NEFA, adiponectin and insulin were analysed in serum. Visceral adipose tissue and liver were weighed and liver TAG liver composition was evaluated. Endothelial and vascular functions were assessed in the aorta and small mesenteric arteries by response to acetylcholine, sodium nitroprusside and phenylephrine (Phe); NO participation was evaluated after incubation with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and endothelial NOS protein expression by Western blotting. PLC decreased body-weight gain, food intake, adiposity, insulin serum concentration and TAG liver content and improved insulin resistance. Aortae from OZR receiving either vehicle or PLC exhibited a lower contractile response to Phe. PLC-treated OZR showed an enhanced release of endothelial NO upon the adrenergic stimulation. The protection of vascular function found after treatment with PLC in an animal model of insulin resistance supports the necessity of clinical trials showing the effect of L-carnitine supplements on metabolic disorders.
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PMID:Oral supplementation of propionyl-l-carnitine reduces body weight and hyperinsulinaemia in obese Zucker rats. 1954 58

Sympathetic nervous system activation is a hallmark of several conditions associated with an adverse prognosis, including hypertension and the metabolic syndrome. Proposed mediators of increased sympathetic drive include hyperinsulinaemia, leptin, NEFAs (non-esterified fatty acids), pro-inflammatory cytokines, baroreflex impairment and others. The role of NEFAs appears to be of particular importance given the increased levels observed in human obesity and the experimental results linking the NEFA-induced pressor response to sympathetic activation. Findings from human studies have yielded conflicting results with regards to a sympathetically mediated association between NEFAs and elevated arterial blood pressure. In the present issue of Clinical Science, Florian and Pawelczyk present some interesting results obtained from a small number of healthy normotensive lean volunteers who were exposed to NEFA infusion and cardiovascular and sympathetic monitoring using state of the art methodology that appears to be in support of such a link. However, several methodological and conceptual considerations need to be taken into account when interpreting the results from this study. Put into perspective, the case for a substantial sympathetically mediated pressor response to NEFA infusion does not appear to be a very strong one.
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PMID:Central sympathetic outflow to skeletal muscle: the major link between non-esterified fatty acids and elevated blood pressure? 1942 44

Chronic elevation of NEFAs (non-esterified fatty acids) due to insulin resistance and obesity has been shown to be associated with increased beta-cell apoptosis and with the aetiology of the reduced beta-cell mass of Type 2 diabetes. SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase) have been implicated in the control of apoptosis. C-K [compound K; 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol] is the main intestinal bacterial metabolite of protopanaxadiol ginsenosides. Currently, little is known about the effects of C-K on beta-cells with the presence of NEFAs. The aim of the present study was to investigate the in vitro protective effect of C-K on MIN6N8 mouse insulinoma beta-cells against NEFA-induced apoptosis, as well as the modulating effect on SAPK/JNK activation. Our results have shown that C-K inhibited the palmitate-induced apoptosis through modulating SAPK/JNK activation. We conclude that C-K protects against beta-cell death and that, by anti-apoptotic activity, C-K may contribute to the previously reported anti-diabetic actions of ginseng.
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PMID:Compound K protects MIN6N8 pancreatic beta-cells against palmitate-induced apoptosis through modulating SAPK/JNK activation. 1994 45


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