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

Obesity is a risk factor for hepatocellular carcinoma (HCC) complicated with alcoholic liver disease (ALD) and cryptogenic cirrhosis. Leptin is a 16-kDa antiobesity hormone secreted mainly by adipocytes. The role of leptin on alcohol-mediated effects in cell line is yet to be unraveled. Therefore, we investigated the effect of leptin against ethanol-elicited cytoxicity in human hepatoma cell lines (HepG2). HepG2 cells were treated with leptin (31.2 nM), ethanol (500 mM), ethanol+leptin and untreated cells served as control. 48 h after treatment, cell viability, apoptosis, TNF-alpha secretory response and oxidative damage were analysed. Our results suggest that leptin at a concentration of 31.2 nM prevents ethanol elicited cytotoxicity as evidenced by MTT and trypan blue dye exclusion assay. Leptin also inhibited ethanol-induced apoptosis, which was confirmed by [(3)H] thymidine uptake and cell cycle analysis using propidium iodide (PI) staining. Further, simultaneous leptin treatment along with ethanol showed protection against ethanol mediated cellular damage as indicated by significantly decreased levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) and significantly increased levels of reactive nitrogen species (RNS), reduced glutathione (GSH) and elevated activities of superoxide dismutase (SOD) and catalase (CAT). In addition, leptin downregulated the secretion of tumor necrosis factor-alpha (TNF-alpha) by ethanol-induced HepG2 cells. Our results demonstrate that simultaneous leptin treatment along with ethanol could be useful in preventing the damage produced by ethanol, which might be of therapeutic interest.
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PMID:Mouse recombinant leptin protects human hepatoma HepG2 against apoptosis, TNF-alpha response and oxidative stress induced by the hepatotoxin-ethanol. 1754 59

Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as superoxide dismutase, catalase, and the glutathione peroxidase and thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve recovery from ischemia-reperfusion injury. This review summarises the role of myocardial antioxidant enzymes in ischemia-reperfusion injury, particularly the glutathione peroxidase (GPX) and the thioredoxin reductase (TxnRed) systems. GPX and TxnRed are selenocysteine dependent enzymes, and their activity is known to be dependent upon an adequate supply of dietary selenium. Moreover, various studies suggest that the supply of selenium as a cofactor also regulates gene expression of these selenoproteins. As such, dietary selenium supplementation may provide a safe and convenient method for increasing antioxidant protection in aged individuals, particularly those at risk of ischemic heart disease, or in those undergoing clinical procedures involving transient periods of myocardial hypoxia.
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PMID:Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review. 1758 62

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 microg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 microg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements.
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PMID:Maternal-foetal status of copper, iron, molybdenum, selenium and zinc in obese gestational diabetic pregnancies. 1772 48

The aim of this study was to determinate both the oxidative stress/anti-oxidative defense status and the concentration of leptin in obese, overweight and normal weight type 2 diabetes mellitus patients to seek possible association between oxidative stress and hyperleptinemia. Oxidative stress status parameters [thiobarbituric acid-reacting substances (TBARS), superoxide anion (O(2)(-)), superoxide dismutase (SOD) activity and total sulphydryl groups] and the concentration of leptin were measured in 312 subjects (178 patients and in 134 control subjects). Obese patients had a significantly higher concentration of leptin compared to obese subjects in the control population (P<0.001). They also had significantly higher plasma concentrations of TBARS, O(2)(-) and SOD activity in combination with a lower sulphydryl group concentration when compared to control subjects. Obese patients had significantly higher concentrations of both TBARS and O(2)(-) and increased SOD activity compared to normal weight patients. The odds ratio for the degree of association between oxidative stress status parameters and hyperleptinemia was strongest for TBARS [odds ratio 2.66, 95% CI (1.02-6.94), P=0.045]. The observed positive correlation between TBARS and leptin (rho=0.29, P<0.01) in obese patients suggests that increased oxidative stress and hyperleptinemia, both consequences of obesity, may play a role in type 2 diabetes mellitus development.
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PMID:The influence of obesity on the oxidative stress status and the concentration of leptin in type 2 diabetes mellitus patients. 1785 Sep 13

The objective of this paper is to evaluate adaptations in hepatic mitochondrial protein mass, function and efficiency in a rat model of high-fat diet-induced obesity and insulin resistance that displays several correlates to human obesity. Adult male rats were fed a high-fat diet for 7 weeks. Mitochondrial state 3 and state 4 respiratory capacities were measured in liver homogenate and isolated mitochondria by using nicotinamide adenine dinucleotide, flavin adenine dinucleotide and lipid substrates. Mitochondrial efficiency was evaluated by measuring proton leak kinetics. Mitochondrial mass was assessed by ultrastructural observations and citrate synthase (CS) activity measurements. Mitochondrial oxidative damage and antioxidant defence were also considered by measuring lipid peroxidation, aconitase and superoxide dismutase (SOD) specific activity. Whole body metabolic characteristics were obtained by measuring 24-h oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and nonprotein respiratory quotient (NPRQ), using indirect calorimetry with urinary nitrogen analysis. Whole body glucose homeostasis was assessed by measuring plasma insulin and glucose levels after a glucose load. Adult rats fed a high-fat diet for 7 weeks, exhibit not only obesity, insulin resistance and hepatic steatosis, but also reduced respiratory capacity and increased oxidative stress in liver mitochondria. Our present results indicate that alterations in the mitochondrial compartment induced by a high-fat diet are associated with the development of insulin resistance and ectopic fat storage in the liver. Our results thus fit in with the emerging idea that mitochondrial dysfunction can led to the development of metabolic diseases, such as obesity, type 2 diabetes mellitus and nonalcoholic steatohepatitis.
Obesity (Silver Spring) 2008 May
PMID:Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance. 1827 91

Factors responsible for presbyacusis include physiological ageing processes as well as endogenous or exogenous causes. In the industrial countries, two main exogenous causes are exposure to loud noise and obesity. Pathomechanisms contributing to presbyacusis are hypoxia/ischemia, reactive species formation and oxidative stress, apoptotic and necrotic death of hair cells and spiral ganglion cells as well as inherited and acquired mutations in the mitochondrial DNA. Important for the successful treatment of presbyacusis is a timely fitting of hearing aids on both ears to improve communication and provide the auditory system with acoustic information. Using the hearing aids will also elevate the detection threshold of an existing tinnitus signal. At present, several therapeutic strategies based on pharmacological intervention are under discussion. The application of antioxidants or caloric restriction are considered to prevent or reduce oxidative stress-induced damage. Animal experiments evidenced that superoxide dismutase 2 (SOD2) strongly decreases in age; thus, a further approach may be the overexpression or modulation of the SOD2 within the cochlea. Adenoviral-mediated gene transfer technology would be a tempting approach to address this type of therapy. Finally, hair cell regeneration could be a possible treatment of presbyacusis in the future.
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PMID:[Pathogenesis and treatment of presbyacusis. Current status and future perspectives]. 1833 47

To understand whether oxidants contribute to the initiation and/or promulgation toward aging, the present study has been undertaken on 220 healthy male volunteers aged 20-80 years selected from the defined electoral area (suburbs of Tirupati, Andhra Pradesh, India) to evaluate the concentrations of free radicals (superoxide anion, hydrogen peroxide), lymphocyte antioxidant enzymes (glutathione S-transferase, superoxide dismutase, catalase), and DNA damage in relation to obesity and smoking (lifestyles). A two fold increase of lymphocyte free radical generation (DNA damage) was observed in older age groups with a reduced antioxidant potential, forming a link between cigarette smoking and oxidative stress represented by an antioxidant imbalance. Body mass index had a positive relationship with oxidative stress, but antioxidant levels did not vary with body mass index. The findings conclude that free radical-mediated oxidative stress and DNA damage accelerate with lifestyle variations under reduced antioxidant potential.
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PMID:Age-related correlation between antioxidant enzymes and DNA damage with smoking and body mass index. 1842 59

Insulin resistance and hyperinsulinemia are commonly present in obesity and pre-diabetes, and hyperinsulinemia is both a marker and a cause for insulin resistance. However, the molecular link between hyperinsulinemia and insulin resistance remains elusive. The present study examined the effect of chronic insulin treatment on the reactive oxygen species (ROS) production, insulin signalling and insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The results showed that chronic insulin treatment significantly increased the intracellular generation of superoxide anion, hydrogen peroxide and hydroxyl radical. ROS induced by chronic insulin treatment inhibited insulin signalling and glucose uptake, induced endoplasmic reticulum (ER) stress and JNK activation. Furthermore, these effects were reversed by antioxidants N-acetylcysteine, superoxide dismutase or catalase. These results suggested that ROS, ER stress and JNK pathway are involved in insulin resistance induced by chronic insulin treatment. Therefore, oxidative stress could be a potential interventional target for hyperinsulinemia-induced insulin resistance and related diseases.
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PMID:Chronic insulin treatment causes insulin resistance in 3T3-L1 adipocytes through oxidative stress. 1856 16

Adipocytokines may be the molecular link between obesity and vascular disease. However, the effects of these factors on coronary vascular function have not been discerned. Accordingly, the goal of this investigation was to delineate the mechanisms by which endogenous adipose-derived factors affect coronary vascular endothelial function. Both isolated canine coronary arteries and coronary blood flow in anesthetized dogs were studied with and without exposure to adipose tissue. Infusion of adipose-conditioned buffer directly into the coronary circulation did not change baseline hemodynamics; however, endothelial-dependent vasodilation to bradykinin was impaired both in vitro and in vivo. Coronary vasodilation to sodium nitroprusside was unaltered by adipose tissue. Oxygen radical formation did not cause the impairment because quantified dihydroethidium staining was decreased by adipose tissue and neither a superoxide dismutase mimetic nor catalase improved endothelial function. Inhibition of nitric oxide (NO) synthase with L-NAME diminished bradykinin-mediated relaxations and eliminated the subsequent vascular effects of adipose tissue. In vitro measurement of NO demonstrated that adipose tissue exposure quickly lowered baseline NO and abolished bradykinin-induced NO production. The results indicate that adipose tissue releases factor(s) that selectively impair endothelial-dependent dilation via inhibition of NO synthase-mediated NO production.
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PMID:Endogenous adipose-derived factors diminish coronary endothelial function via inhibition of nitric oxide synthase. 1857 44

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.
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PMID:Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. 1933 85


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