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

Rising youth obesity is a serious public health concern. There is a widespread view that declining physical activity is contributing to this trend. A total of 929 young South Australians (age=9-15 years) were surveyed in 1985 and 2004 on usual physical activity in several contexts, including attitudes to physical activity. Eight of 10 South Australian schools participating in the 1985 Schools Health and Fitness Survey were revisited in 2004. Comparisons were made on: organised sport, active transport, physical education (PE), playground activity, vigorous physical activity (VPA), total leisure-time physical activity (LTPA), and attitudes to PE and school sport. The questionnaire and method of administration were identical in both surveys. There were no differences between surveys in club and school sport participation, walking to school, and reported enjoyment of PE and school sport. In 2004 fewer children rode to school, but PE classes were more frequent. The percentage of children who 'sit and talk' during school breaks had increased, with a decreased percentage of older girls who 'run around' during school breaks. There was a significantly higher LTPA in MET.min in 2004 for boys, which was particularly evident at higher percentiles. There were no changes in mean or distribution of LTPA for the whole sample or girls. The percentage of respondents reporting >/=3 bouts of VPA in the previous week rose from 51% (1985) to 76% (2004). There is no consistent evidence of declining physical activity among South Australian youth. It is apparent that physical activity in some contexts has declined, while in other contexts levels are the same or higher than in 1985. This underscores the complex nature of physical activity and the influences on this behaviour.
 ...
PMID:Trends in physical activity behaviours and attitudes among South Australian youth between 1985 and 2004. 1733 54

Abnormal dietary intake of macronutrients is implicated in the development of obesity and fatty liver disease. Steatosis develops in cultured hepatocytes exposed to medium containing either a high concentration of long chain free fatty acids (HFFA) or medium deficient in methionine and choline (MCD). This study examined the mitochondrial reactive oxygen species (ROS)-dependent regulation of the phosphoinositol (PI) 3-kinase pathway in steatosis induced by exposure of AML-12 mouse hepatocytes to MCD or HFFA medium. Exposure to either MCD or HFFA medium resulted in increased production of superoxide anions and H(2)O(2), transduction of the PI 3-kinase pathway and steatosis. Inhibition of PI 3-kinase with LY294002 prevented steatosis. Pharmacologically inhibiting electron transport chain complex III production of ROS prevented activation of PI 3-kinase during macronutrient perturbation, whereas pharmacologically promoting electron transport chain complex III ROS production activated PI 3-kinase independent of nutrient input. The data suggest that H(2)O(2) is the ROS species involved in signal transduction; promoting the rapid conversion of superoxide to H(2)O(2) does not inhibit PI 3-kinase pathway activation during nutrient perturbation, and exogenous H(2)O(2) activates it independent of nutrient input. In addition to transducing PI 3-kinase, the ROS-dependent signal cascade amplifies the PI 3-kinase signal by maintaining phosphatase and tensin homolog in its inactive phosphorylated state. Knockdown of phosphatase and tensin homolog by small interfering RNA independently activated the PI 3-kinase pathway. Our findings suggest a common path for response to altered nutrition involving mitochondrial ROS-dependent PI 3-kinase pathway regulation, leading to steatosis.
 ...
PMID:Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway. 1754 Jul 68

Obesity and insulin resistance are the key factors for progression of hepatic fibrosis in various chronic liver diseases including non-alcoholic steatohepatitis (NASH). Recently it has been shown that leptin plays a pivotal role in development of hepatic fibrosis. Leptin promotes hepatic fibrogenesis through upregulation of transforming growth factor-beta in Kupffer cells and sinusoidal endothelial cells. Further, leptin facilitates proliferation and prevents apoptosis of hepatic stellate cells. There is a paradox, however, in that ob/ob mice and Zucker rats, which are the obese and diabetic strains, had minimal profibrogenic responses in the liver, most likely because they lack leptin and its receptors. To establish a more clinically relevant model to study the mechanism of fibrogenesis under steatohepatitis, fatty changes and profibrogenic responses in the liver caused by methionine-choline deficiency (MCD) were investigated in the KK-A(y) mouse, which is an obese and diabetic strain. KK-A(y) mice developed more severe hepatic steatosis, inflammation and fibrosis induced by an MCD diet as compared to C57Bl/6 controls. Importantly, KK-A(y) mice lack physiological upregulation of adiponectin levels, suggesting that adiponectin plays a pivotal role not only in regulation of insulin sensitivity but also in modulation of inflammatory and profibrogenic responses in dietary steatohepatitis. Collectively, these findings support the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic fibrosis in the setting of steatohepatitis.
 ...
PMID:Role of adipocytokines in hepatic fibrogenesis. 1756 76

Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-beta, alpha 1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis.
 ...
PMID:Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects. 1850 44

Blockade of brain melanin-concentrating hormone 1 receptor (MCH1R) significantly ameliorates fatty liver as well as obesity. However, the mode of action of this effect is unknown. This study examined the effect of a MCH1R antagonist in murine steatohepatitis models with and without obesity and clarified whether these pharmacological effects were attributed to anti-obesity effects. Steatohepatitis with concomitant obese phenotypes was developed after 52-week exposure to a high-fat diet, and steatohepatitis with reduced body weight was developed by exposure to a methionine- and choline-deficient diet for 10 days. Chronic intracerebroventricular infusion of a peptidic MCH1R antagonist reduced hepatic triglyceride contents and ameliorated steatohepatitis on histological observations in both mice models. Improvement of steatohepatitis was concomitant with amelioration of obese phenotypes such as hyperinsulinemia and hyperleptinemia in the case of the obese model, whereas body weight reduction was not associated with amelioration of steatohepatitis by the antagonist in the lean model. Reduction of hepatic gene expressions encoding cytochromes P450 4A was identified by treatment with the antagonist in both the obese and lean models. These results suggest that brain blockade of MCH1R could alleviate steatohepatitis independently from anti-obesity effects. In conclusion, MCH1R antagonist could have a new therapeutic potential for the treatment of human nonalcoholic steatohepatitis.
 ...
PMID:Antagonism of central melanin-concentrating hormone 1 receptor alleviates steatohepatitis in mice. 1852 32

Factors influencing circulating estrogen levels, insulin-mediated pathways or energy balance through obesity-related mechanisms, such as physical activity, have been proposed as potential risk factors for endometrial cancer. We examined measures of physical activity in relation to endometrial cancer risk in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, a prospective study of cancer incidence and mortality, using information obtained at baseline in 1992. From 1992 to 2003, 466 incident endometrial cancers were identified among 42,672 postmenopausal women with intact uteri who were cancer-free at enrollment. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) while adjusting for potential confounders. To assess the role of body mass index (BMI) in this relationship, we computed multivariate RR with and without adjustment for BMI and stratifying by BMI. All measures of physical activity and the avoidance of sedentary behavior were associated with lower endometrial cancer risk. Baseline recreational physical activity was associated with 33% lower risk (RR = 0.67, 95% CI 0.44-1.03 for 31.5+ vs. <7 MET-hr/week, trend p = 0.007) in the multivariate model without BMI. However, the trend was attenuated after further adjustment for BMI (trend p = 0.18). BMI significantly modified the association between physical activity and endometrial cancer risk (heterogeneity of trends p = 0.01). The inverse relationship was seen only among overweight or obese women (trend p = 0.003) and not in normal weight women (trend p = 0.51). In summary, light and moderate physical activity including daily life activities were associated with lower endometrial cancer risk in our study, especially among women who are overweight or obese.
 ...
PMID:The role of body weight in the relationship between physical activity and endometrial cancer: results from a large cohort of US women. 1865 69

It has been demonstrated that human melanocortin-4 receptor (hMC4R) plays an important role in the control of energy homeostasis, and heterozygous mutations in the hMC4R gene are the most frequent genetic cause of severe human obesity. In order to obtain additional insight into the structure and function, we cloned, expressed, and purified the second transmembrane domain of the wild-type hMC4R (wt-TM2) and D90N mutant hMC4R (m-TM2). To facilitate structural studies of these hMC4R by solid-state NMR, efficient methods for the production of milligram quantities of isotopically labeled protein are necessary. However, large-scale production of most transmembrane proteins has been limited by experimental adversities due to insufficient yields and low solubility of protein. Nevertheless, through the optimization of the expression and purification approach, we could obtain uniformly or selectively labeled fusion proteins in yields as high as 200-250 mg per liter M9 minimal medium. These proteins were overexpressed in inclusion bodies as a fusion protein with ketosteroid isomerase (KSI) in Escherichia coli, and the fusion protein was purified using immobilized metal affinity chromatography under denaturing conditions. wt-/m-TM2 peptides were released from the fusion by cyanogen bromide cleavage at the Met residue and separated from the carrier KSI by size exclusion chromatography. Initial structural data obtained by solution NMR measurements of wt-/m-TM2 is also presented. The successful application to the production of the second transmembrane domain of human MC4R indicates that the method can be applied to other transmembrane proteins as well and also enable its structural and functional studies using solid-state NMR spectroscopy.
 ...
PMID:High-level expression and purification of the second transmembrane domain of wild-type and mutant human melanocortin-4 receptor for solid-state NMR structural studies. 1880 99

A lot of epidemiological studies have shown that physical activity can prevent the development of chronic diseases such as obesity, diabetes, osteoporosis, cardiovascular diseases and cancer Physical activity can be classified by rate of energy expenditure: light intensity 1-3 METs, moderate 3-6 MET's, vigorous 6-9 MET's, very vigorous >9 MET's. Although it is evident that an active lifestyle has many health benefits and sedentary habits are associated with an increased risk of chronic diseases, the debate still continues as to how much, what type, how often, at what intensity physical activity should be performed to have a positive effect on the health. Reduction of cardiovascular risk is observed already with a moderate intensity physical activity (3-6METs); whilst to improve physical fitness training must be more vigorous (6-9 METs). In conclusion good goals are achieved when moderate levels of physical activity are performed on a regular basis (at least 3- 5 days a week for 30 minutes). But to reach also countable results on body weight control the frequency should be 5-7 days a week for 60 minutes.
 ...
PMID:[Importance of physical activity for prevention of chronic diseases]. 1906 54

Population studies provide evidence that obesity and insulin resistance are associated not only with elevated serum insulin levels and reduced serum adiponectin levels but also with increased risk of aggressive prostate and colon cancer. We show here that adiponectin activates AMP-activated protein kinase (AMPK) in colon (HT-29) and prostate (PC-3) cancer cells. These results are consistent with prior observations in myocytes, but we show that in epithelial cancer cells AMPK activation is associated with reduction in mammalian target of rapamycin activation as estimated by Ser(2448) phosphorylation, with reduction in p70S6 kinase activation as estimated by Thr(389) phosphorylation, with ribosomal protein S6 activation as estimated by Ser(235/236) phosphorylation, with reduction in protein translation as estimated by [(35)S]methionine incorporation, and with growth inhibition. Adiponectin-induced growth inhibition is significantly attenuated when AMPK level is reduced using small interfering RNA, indicating that AMPK is involved in mediating the antiproliferative action of this adipokine. Thus, adiponectin has the characteristics of a AMPK-dependent growth inhibitor that is deficient in obesity, and this may contribute to the adverse effects of obesity on neoplastic disease. Furthermore, metformin was observed to activate AMPK and to have growth inhibitory actions on prostate and colon cancer cells, suggesting that this compound may be of particular value in attenuating the adverse effects of obesity on neoplasia.
 ...
PMID:The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. 1913 81

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.
 ...
PMID:Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity. 1915 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>