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)

Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors.
 ...
PMID:Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B. 1923 34

The coexistence of intrauterine and neonatal malnutrition and the development of obesity, type 2 diabetes and related comorbidities have been confirmed in a number of studies in humans and animal models. Data from studies in animals suggest that epigenetic changes as a result of altered methylation of the genomic DNA may be responsible for such metabolic patterning. Methionine, an essential amino acid, plays a critical role in the methyltranferases involved in the methylation by providing the one-carbon units via the methionine transmethylation cycle. Because of its interaction with a number of vitamins (B12, folate, pyridoxine), its regulation by hormones, i.e. insulin and glucagon, and by the changes in redox state, methionine metabolism is effected by nutrient and environmental influences and by altered physiological states. In the present review the impact of human pregnancy, dietary protein restriction and fatty liver disease on methionine metabolism is discussed. The role of methionine in metabolic programming in a commonly used model of intrauterine growth retardation and in propagation of fatty liver disease is briefly described.
 ...
PMID:Metabolism of methionine in vivo: impact of pregnancy, protein restriction, and fatty liver disease. 1934 72

Canada's Physical Activity Guide to Healthy Active Living (CPAG) is the national reference for messaging on physical activity for health benefits, yet few studies have examined population activity levels in relation to its recommendations. As part of the province-wide in motion initiative, we obtained a baseline measurement of the physical activity levels of adult Manitobans. Physical activity levels were benchmarked against CPAG recommendations and were compared with criteria used in previous surveys. A stratified random sample of adults from the 9 Regional Health Authorities outside of Winnipeg, and from the 12 Community Areas within the Winnipeg Health Region, was surveyed by telephone. Respondents (n = 6,536) reported all light, moderate, and vigorous physical activity of 10 min or more in the previous week. Intensity levels were corrected to reflect standard MET equivalents, using the Ainsworth Compendium. A total of 69.5% of respondents met the minimum CPAG requirements; however, only 29.1% of those did so with vigorous activity. Relative to energy expenditure, 18.3% were classified as inactive (<1.50 kcal.kg-1.day-1 (KKD)), 16.4% as moderately active (1.50 to 2.99 KKD), and 65.3% as active (>or=3.00 KKD). When assessed against the CPAG recommendations, which promote integration of physical activity into one's daily routine, a higher proportion of Manitobans met recommended physical activity levels than that reported in previous surveys, which focused on leisure activity. Given the corresponding increase in levels of obesity and chronic disease, and equivocal nutrient intake data, we recommend that the CPAG recommendations be reviewed, especially with respect to the inclusion of routine baseline activities of daily living.
 ...
PMID:Canada's physical activity guide recommendations are a low benchmark for Manitoba adults. 1937 47

The eating disorders anorexia and bulimia nervosa have traditionally been regarded as entirely separate from obesity. Eating disorders have been regarded as Western culture-bound syndromes, arising in societies with excessive emphasis on weight, shape and appearance, and best treated by psychological therapies, in particular cognitive behavioural therapy or family-based interventions. In contrast, obesity has been considered a medical illness with metabolic and genetic origins, and thought to be best treated by mainstream medicine, involving dietary, drug or surgical treatment. We believe that this polarisation is fundamentally flawed, and research and treatment of both types of disorder would be better served by greater appreciation of the psychosocial components of obesity and the biological and genetic components of eating disorders. There are similarities in phenotype (such as excessive attempts at weight control, binge eating behaviours) and in risk factors (such as low self-esteem, external locus of control, childhood abuse and neglect, dieting, media exposure, body image dissatisfaction, weight-related teasing and shared susceptibility genes). One example of shared genetic risk is the brain-derived neurotrophic factor (BNDF) gene, in which the valine allele of the Val66Met amino acid polymorphism predisposes to obesity, whereas the methionine allele predisposes to eating disorders. Thus the evidence suggests that these disorders will have both shared and distinct susceptibility factors; some will predispose to both types of disorder, some will push in opposite directions, and some will separate them.
 ...
PMID:Eating disorders and obesity: two sides of the same coin? 1952 39

Metabolic disturbances such as dyslipidemia, lipodystrophy syndrome, visceral obesity, hyperlactatemia, diabetes mellitus, and hepatic steatosis have been recognized as serious complications in long-term antiretroviral-treated HIV-infected patients. The oxidative capacity of liver mitochondria plays a central role in their pathogenesis and can be analyzed using the [(13)C]methionine breath test. We analyzed hepatic mitochondrial function using the [(13)C]methionine breath test in antiretrovirally treated and untreated HIV-infected patients as well as HIV-negative controls. Patients with hepatic steatosis, hypertriglyceridemia, lipohypertrophy, and older age showed reduced methionine metabolism. Hepatic mitochondrial function is impaired in antiretroviral-treated HIV-infected patients with disturbances of lipid metabolism.
 ...
PMID:[(13)C]Methionine breath test as a marker for hepatic mitochondrial function in HIV-infected patients. 2000 11

The prevalence of colorectal cancer is increasing in Asia. However, the age-standardized rate has reached a plateau in some countries. Some studies have shown a male predominance difference and increasing risk in the elderly, but not in the younger population. 'Right shifting' of colorectal cancer, not accountable by difference in age or the indications for endoscopic examination, has also been noted. Westernized diet is associated with colorectal cancer, but controversy remains on how it causes colorectal cancer. Alcohol consumption, obesity, diabetes mellitus, consumption of red and processed meat and cigarette smoking are linked to bowel cancer epidemiologically. Only high dietary calcium has a consistent negative (or 'protective') effect. The efficacy of fish oil, vitamin D, soy, phytoestrogens, folate, methionine, riboflavin and vitamin B6 has not been established. Aspirin and non-steroidal anti-inflammatory drugs use decrease risk of colorectal cancer after 5-10 years of use. There is no evidence for a detrimental effect of proton pump inhibitors or benefit of statins in colorectal cancer. In conclusion, there is a rising trend and prevalence of colorectal cancer in Asia. Dietary modification or supplementation may not be effective in preventing colorectal cancer. Surveillance of colorectal cancer in high-risk groups, according to current recommendation, is probably most effective.
 ...
PMID:Epidemiology of colorectal cancer in Asia. 2000 40

Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content in humans. Here we examined the effect of the I148M substitution on the enzymatic activity and cellular location of PNPLA3. Structural modeling predicted that the substitution of methionine for isoleucine at residue 148 would restrict access of substrate to the catalytic serine at residue 47. In vitro assays using recombinant PNPLA3 partially purified from Sf9 cells confirmed that the wild type enzyme hydrolyzes emulsified triglyceride and that the I148M substitution abolishes this activity. Expression of PNPLA3-I148M, but not wild type PNPLA3, in cultured hepatocytes or in the livers of mice increased cellular triglyceride content. Cell fractionation studies revealed that approximately 90% of wild type PNPLA3 partitioned between membranes and lipid droplets; substitution of isoleucine for methionine at position 148 did not alter the subcellular distribution of the protein. These data are consistent with PNPLA3-I148M promoting triglyceride accumulation by limiting triglyceride hydrolysis.
 ...
PMID:A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. 2003 33

Brain-derived neurotrophic factor (BDNF) regulates food intake and energy metabolism. It has also been suggested that mutations in the human BDNF gene and its receptor TrkB account for disturbed eating and obesity. The Met-allele of the BDNF Val66Met polymorphism has been associated with eating disorders, but the underlying mechanism of its contribution is not known. We report herewith that the effect of BDNF Val66Met polymorphism on binge eating in adolescent girls is dependent on severe food restriction. The scores on EDI-2 Bulimia subscale were significantly higher in BDNF Met-allele carriers who made attempts to regulate their body weight by reducing their meal frequency or by starving. This finding may help to explain why some people develop binge eating in response to dieting and others do not.
 ...
PMID:Food restriction leads to binge eating dependent upon the effect of the brain-derived neurotrophic factor Val66Met polymorphism. 2053 7

Epidemiological studies have clearly shown that whole-grain cereals can protect against obesity, diabetes, CVD and cancers. The specific effects of food structure (increased satiety, reduced transit time and glycaemic response), fibre (improved faecal bulking and satiety, viscosity and SCFA production, and/or reduced glycaemic response) and Mg (better glycaemic homeostasis through increased insulin secretion), together with the antioxidant and anti-carcinogenic properties of numerous bioactive compounds, especially those in the bran and germ (minerals, trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols), are today well-recognised mechanisms in this protection. Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses. The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as alpha-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid also deserve to be studied in more depth. Finally, benefits of nutrigenomics to study complex physiological effects of the 'whole-grain package', and the most promising ways for improving the nutritional quality of cereal products are discussed.
 ...
PMID:New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? 2056 94

Besides cardiovascular disease, a high salt intake causes other adverse health effects, i.e., gastric and some other cancers, obesity (risk factor for many cancer sites), Meniere's disease, worsening of renal disease, triggering an asthma attack, osteoporosis, exacerbation of fluid retention, renal calculi, etc. Diets containing high amounts of food preserved by salting and pickling are associated with an increased risk of cancers of the stomach, nose and throat. Because gastric cancer is still the most common cancer in some countries (especially in Japan), its prevention is one of the most important aspects of cancer control strategy. Observations among Japanese immigrants in the U.S.A. and Brazil based on the geographic differences, the trend in cancer incidence with time, and change in the incidence patterns indicate that gastric cancer is closely associated with dietary factors such as the intake of salt and salted food. The findings of many epidemiological studies suggest that high dietary salt intake is a significant risk factor for gastric cancer and this association was found to be strong in the presence of Helicobacter (H.) pylori infection with atrophic gastritis. A high-salt intake strips the lining of the stomach and may make infection with H. pylori more likely or may exacerbate the infection. Salting, pickling and smoking are traditionally popular ways of preparing food in Japan and some parts of Asia. In addition to salt intake, cigarette smoking and low consumption of fruit and vegetables increase the risk of stomach cancer. However, it is not known whether it is specifically the salt in these foods or a combination of salt and other chemicals that can cause cancer. One study identified a mutagen in nitrite-treated Japanese salted fish, and chemical structure of this mutagen suggests that it is derived from methionine and that salt and nitrite are precursors for its formation. Working under conditions of heat stress greatly increased the workers' salt excretion through perspiration. Workers exposed to heat stress consumed as much as 13-38 g salt daily. As salt strongly enhances and promotes chemical gastric carcinogenesis and H. pylori infection in both humans and animals, there is an association between work, salt intake, and development of stomach cancer. Reducing salt intake, especially during pregnancy, also reduces the risk of developing breast cancer and many other diseases, as well as obesity. The risk of most cancers is reduced by losing weight. The geographical data and analyses currently available suggest that road salt (road salting in winter) may be associated with elevated mortality from cancer of the breast, lung, esophagus, throat, larynx, large intestine, rectum and bladder. There is no available literature on the health impacts of road salt. The cause and effect relationships cannot be established without further studies.
 ...
PMID:[Salt and cancer]. 2064 83


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