Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies report on the association between obesity and oxidative stress, with and without additional diseases. Macrophages in adipocytes, and hypoxia in adipose tissue have been suggested to explain how obesity can relate to oxidative stress. The straight line hypothesis using the lactic acid trap construct has been put forward to explain how proton imbalance can relate to obesity. Proton imbalance has been also reported to associate with the production of reactive oxygen species by inhibition of mitochondrial energy production. This review brings together existing literature and concepts to explain how obesity can relate to oxidative stress via protons, uniquely for itself or, as often observed, in conglomeration of additional diseases.
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PMID:The straight line hypothesis elaborated: case reference obesity, an argument for acidosis, oxidative stress, and disease conglomeration? 2018 34

Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55-0.65 mM), by the following chemical reaction; Mg + 2H(2)O --> Mg (OH)(2) + H(2). The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.
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PMID:Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. 2021 47

Recent studies have unequivocally associated the fat mass and obesity-associated (FTO) gene with the risk of obesity. In vitro FTO protein is an AlkB-like DNA/RNA demethylase with a strong preference for 3-methylthymidine (3-meT) in single-stranded DNA or 3-methyluracil (3-meU) in single-stranded RNA. Here we report the crystal structure of FTO in complex with the mononucleotide 3-meT. FTO comprises an amino-terminal AlkB-like domain and a carboxy-terminal domain with a novel fold. Biochemical assays show that these two domains interact with each other, which is required for FTO catalytic activity. In contrast with the structures of other AlkB members, FTO possesses an extra loop covering one side of the conserved jelly-roll motif. Structural comparison shows that this loop selectively competes with the unmethylated strand of the DNA duplex for binding to FTO, suggesting that it has an important role in FTO selection against double-stranded nucleic acids. The ability of FTO to distinguish 3-meT or 3-meU from other nucleotides is conferred by its hydrogen-bonding interaction with the two carbonyl oxygen atoms in 3-meT or 3-meU. Taken together, these results provide a structural basis for understanding FTO substrate-specificity, and serve as a foundation for the rational design of FTO inhibitors.
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PMID:Crystal structure of the FTO protein reveals basis for its substrate specificity. 2037 3

Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure. We investigated this relationship and its modification by hyperglycemia and oxidative stress in a population-based cohort of elderly subjects with normal glucose metabolism (n=267), impaired glucose metabolism (n=189), and type 2 diabetes (n=290). In an age- and sex-adjusted linear regression model, plasma myeloperoxidase was positively associated with systolic blood pressure (2.10 mm Hg per 1 SD increment of myeloperoxidase [95% CI: 0.66 to 3.54]), and this association was stronger at higher levels of fasting glucose (0.61 [-1.70 to 2.93], 1.33 [-1.43 to 4.10], and 3.42 [1.01 to 5.82] for increasing tertiles of glucose) and higher plasma levels of oxidized low-density lipoprotein (0.92 [-1.31 to 3.14], 2.00 [-0.71 to 4.70], and 3.58 [0.98 to 6.19] for increasing tertiles of oxidized low-density lipoprotein). Likewise, the relationship between myeloperoxidase and blood pressure was strongest under conditions associated with oxidative stress, like obesity, low high-density lipoprotein cholesterol, metabolic syndrome, and type 2 diabetes. The strength of these associations was only marginally attenuated by adjustment for other cardiovascular risk factors. Our data demonstrate that myeloperoxidase is positively and independently associated with blood pressure, and this association is strongest in subjects with (hyperglycemia-induced) oxidative stress. These observations, together with emerging evidence that myeloperoxidase-derived oxidants contribute to the initiation and propagation of cardiovascular disease, identify myeloperoxidase as a promising target for drug development.
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PMID:Hyperglycemia and oxidative stress strengthen the association between myeloperoxidase and blood pressure. 2038 72

Epicardial and myocardial fats increase with degree of visceral adiposity and possibly contribute to obesity-associated cardiac changes. Echocardiographic epicardial fat thickness is a new and independent marker of visceral adiposity. The aim of this study was to test whether echocardiographic epicardial fat is related to myocardial fat. Twenty consecutive Caucasian men (body mass index 30.5 +/- 2 kg/m(2), 42 +/- 7 years of age) underwent transthoracic echocardiography for epicardial fat thickness, morphologic and diastolic parameter measurements, hydrogen-1 magnetic resonance spectroscopy for myocardial fat quantification, and magnetic resonance imaging for epicardial fat volume estimation. Hydrogen-1 magnetic resonance spectroscopic myocardial fat content, magnetic resonance imaging of epicardial fat volume, and echocardiographic epicardial fat thickness range varied from 0.5% to 31%, 4.5 to 43 ml, and 3 to 15 mm, respectively. Myocardial fat content showed a statistically significant correlation with echocardiographic epicardial fat thickness (r = 0.79, p <0.01), waist circumference (r = 0.64, p <0.01), low-density lipoprotein cholesterol (r = 0.54, p <0.01), plasma adiponectin levels (r = -0.49, p <0.01), and isovolumic relaxation time (r = 0.59, p <0.01). However, multivariate linear regression analysis showed epicardial fat thickness as the most significant independent correlate of myocardial fat (p <0.001). Although this study is purely correlative and no causative conclusions can be drawn, it can be postulated that increased echocardiographic epicardial fat accumulation could reflect myocardial fat in subjects with a wide range of adiposity.
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PMID:Relation of echocardiographic epicardial fat thickness and myocardial fat. 2053 39

Protein-tyrosine phosphatase 1B (PTP1B) is an attractive drug target for type II diabetes and obesity. The structural motions of its S-loop play crucial roles in WPD-loop closure that is essential for the catalytic mechanism of this protein. In the current studies, totally 20 ns molecular dynamics simulations were employed on both PTP1B and its complex with inhibitors in the explicit solution surroundings with the periodic boundary conditions in order to perform detail exam on the structural flexibility of S-loop. Together with calculating RMSD values and monitoring the distances between active site and the residues in S-loop, it is found that S-loop can move towards to active site and form a tight binding pocket for substrates upon inhibitor binding. And a hydrogen bond network rearrangement was detected in this region, which may cause the transforms of both the tree-dimensional structure and the total accessible surfaces for the residues in S loop. Additionally, the second structures of Ser201 and Gly209 have huge changes for the open system, which is not detected in close system. These findings can reveal the possible mechanism of ligand recognitions and inhibitions, further providing useful information to design novel inhibitors against PTP1B and develop new treatment for type II diabetes and obesity.
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PMID:Structural flexibility and interactions of PTP1B's S-loop. 2064 Aug 40

Adipose tissue mass in mammals is expanding by increasing the average cell volume as well as the total number of the adipocytes. Up-regulation of lipid storage in fully differentiated adipocytes resulting in their enlargement is well documented and thought to be a critical mechanism for the expansion of adipose tissue depots during the growth of both lean and obese animals and human beings. A novel molecular mechanism for the regulation of lipid storage and cell size in rat adipocytes has recently been elucidated for the physiological stimuli, palmitate and hydrogen peroxide, the anti-diabetic sulfonylurea drug, glimepiride, and insulin-mimetic phosphoinositolglycans. It encompasses (i) the release of small vesicles, so-called adiposomes, harbouring the glycosylphosphatidylinositol-anchored (c)AMP-degrading phosphodiesterase Gce1 and 5'-nuceotidase CD73 from large donor adipocytes, (ii) the transfer of the adiposomes and their interaction with detergent-insoluble glycolipid-enriched microdomains of the plasma membrane of small acceptor adipocytes, (iii) the translocation of Gce1 and CD73 from the adiposomes to the intracellular lipid droplets of the acceptor adipocytes and (iv) the degradation of (c)AMP at the lipid droplet surface zone by Gce1 and CD73 in the acceptor adipocytes. In concert, this sequence of events leads to up-regulation of esterification of fatty acids into triacylglycerol and down-regulation of their release from triacylglycerol. This apparent mechanism for shifting the triacylglycerol burden from large to small adipocytes may provide novel strategies for the therapy of metabolic diseases, such as type 2 diabetes and obesity.
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PMID:Control of lipid storage and cell size between adipocytes by vesicle-associated glycosylphosphatidylinositol-anchored proteins. 2088 86

Obesity is linked to systemic oxidative stress and, although brown adipose tissue (BAT) plays a crucial role in energy balance, BAT redox status effects on obesity have not been studied previously. Female rats exhibit a greater BAT thermogenic capacity, attributed to enhanced mitochondrial differentiation, than males. The aim of this study was to investigate whether the mitochondrial sexual dimorphism is related to differences in BAT redox status and to assess its role in the regulation of body weight gain in response to chronic high fat diet (HFD) feeding. Ten-week-old Wistar rats of both genders were fed a pelleted control diet or HFD for 26 weeks. Although mitochondria of female rats produced higher levels of hydrogen peroxide than those of males, females exhibited lower oxidative damage, attributed to greater glutathione peroxidase activity and higher glutathione content. In response to HFD, body weight increased markedly in females, but oxidative capacity increased only in males, thus maintaining improved BAT redox status compared with females. In conclusion, the sexual dimorphism in BAT redox status found in control animals is attenuated by the HFD. The enhanced oxidative capacity of HFD males can be related to their greater resistance to body weight gain.
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PMID:Brown adipose tissue redox status in response to dietary-induced obesity-associated oxidative stress in male and female rats. 2103

In view of a dramatic increase in the incidence of obesity, the present study examined the appetite effects of a functional fiber as a potential dietary intervention. Fiber may increase satiety. Satiety effects also may be linked to colonic fermentation. Short-chain fructooligosaccharide (scFOS) are fermentable fibers that can be added to foods to influence these actions. The primary objective of this study was to determine if scFOS affects satiety and hunger and has an additive effect on food intake. Using a double-blind crossover design, 20 healthy subjects were assigned to consume two separate doses of 0 g, 5 g, or 8 g of scFOS. The first dose was mixed into a hot cocoa beverage and served with a breakfast meal of a bagel and cream cheese. A beverage was used in the test meal due to the ease with which scFOS can be added to this medium. Satiety was assessed with visual analogue scales (VASs) at 0, 15, 30, 45, 60, 90, 120, 180, and 240 min. Ad libitum food intake was measured at a lunch meal provided at the test site at 240 min. Subjects then recorded their food intake over the remainder of the 24-h study day. The second dose of scFOS was consumed in the form of 3 solid, chocolate-flavored chews (51-67 total kcal) without additional food or drink, 2h prior to the subject's dinner meal. Breath hydrogen measures were collected prior to the breakfast test meal (0 min) and the ad libitum lunch (240 min). Gastrointestinal tolerance was evaluated over the course of the 24-h study day using VAS. All treatments were well tolerated. No differences in subjective satiety over the morning, or food intake at lunch, were found. Over the remainder of the day, the high dose of scFOS reduced food intake in women, but increased food intake in men, suggesting a gender difference in the longer-term response. Breath hydrogen, used as a marker of fermentation, increased in a dose-dependent manner. These results indicate that scFOS undergoes fermentation within 240 min; however, acceptable amounts of scFOS did not enhance acute satiety or hunger.
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PMID:Effects of short-chain fructooligosaccharides on satiety responses in healthy men and women. 2114 72

Recent extensive studies have revealed that molecular hydrogen (H(2)) has great potential for improving oxidative stress-related diseases by inhaling H(2) gas, injecting saline with dissolved H(2), or drinking water with dissolved H(2) (H(2)-water); however, little is known about the dynamic movement of H(2) in a body. First, we show that hepatic glycogen accumulates H(2) after oral administration of H(2)-water, explaining why consumption of even a small amount of H(2) over a short span time efficiently improves various disease models. This finding was supported by an in vitro experiment in which glycogen solution maintained H(2). Next, we examined the benefit of ad libitum drinking H(2)-water to type 2 diabetes using db/db obesity model mice lacking the functional leptin receptor. Drinking H(2)-water reduced hepatic oxidative stress, and significantly alleviated fatty liver in db/db mice as well as high fat-diet-induced fatty liver in wild-type mice. Long-term drinking H(2)-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. Moreover, drinking H(2)-water decreased levels of plasma glucose, insulin, and triglyceride, the effect of which on hyperglycemia was similar to diet restriction. To examine how drinking H(2)-water improves obesity and metabolic parameters at the molecular level, we examined gene-expression profiles, and found enhanced expression of a hepatic hormone, fibroblast growth factor 21 (FGF21), which functions to enhance fatty acid and glucose expenditure. Indeed, H(2) stimulated energy metabolism as measured by oxygen consumption. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome.
Obesity (Silver Spring) 2011 Jul
PMID:Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. 2129 45


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