Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0497406 (overweight)
 26,365 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies, such as those on Pima Indians, have shown that metabolic factors are involved in the development of obesity and that being overweight is not simply a result of "sloth and gluttony." However, the environment also affects the development of obesity. Among individuals in a given environment, the variability in body size is influenced by genetically determined responses to that environment. People with a low metabolic rate (adjusted for body size and composition) are prone to weight gain, whereas those with a high level of spontaneous physical activity are less likely to become obese. Similarly, individuals with a high 24-hour respiratory quotient (RQ) are more likely to gain weight than those with a low RQ. Insulin sensitivity (not insulin resistance) is another metabolic predictor of obesity. Genetic linkage studies suggest a number of genes are linked to the development of obesity. By sibling-pair linkage analysis, tumor necrosis factor-alpha (TNF-alpha) was found to be linked to the percentage of body fat, and other studies have shown that fat cell production of TNF-alpha is greater in obese individuals.
 ...
PMID:Metabolic differences and the development of obesity. 767 9

Obesity may be a low-grade systemic inflammatory disease. Overweight and obese children and adults have elevated serum levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and leptin, which are known markers of inflammation and closely associated with cardiovascular risk factors and cardiovascular and non-cardiovascular causes of death. This may explain the increased risk of diabetes, heart disease, and many other chronic diseases in the obese. The complex interaction between several neurotransmitters such as dopamine, serotonin, neuropeptide Y, leptin, acetylcholine, melanin-concentrating hormone, ghrelin, nitric oxide, and cytokines and insulin and insulin receptors in the brain ultimately determines and regulates food intake. Breast-feeding of more than 12 mo is associated with decreased incidence of obesity. Breast milk is a rich source of long-chain polyunsaturated fatty acids (LCPUFAs) and brain is especially rich in these fatty acids. LCPUFAs inhibit the production of proinflammatory cytokines and enhance the number of insulin receptors in various tissues and the actions of insulin and several neurotransmitters. LCPUFAs may enhance the production of bone morphogenetic proteins, which participate in neurogenesis, so these fatty acids might play an important role in brain development and function. It is proposed that obesity is a result of inadequate breast feeding, which results in marginal deficiency of LCPUFAs during the critical stages of brain development. This results in an imbalance in the structure, function, and feedback loops among various neurotransmitters and their receptors, which ultimately leads to a decrease in the number of dopamine and insulin receptors in the brain. Hence, promoting prolonged breast feeding may decrease the prevalence of obesity. Exercise enhances parasympathetic tone, promotes antiinflammation, and augments brain acetylcholine and dopamine levels, events that suppress appetite. Acetylcholine and insulin inhibit the production of proinflammatory cytokines and provide a negative feedback loop for postprandial inhibition of food intake, in part, by regulating leptin action. Statins, peroxisome proliferator-activated receptor-gamma binding agents, non-steroidal antiinflammatory drugs, and infant formulas supplemented with LCPUFAs, and LCPUFAs themselves, which suppress inflammation, may be beneficial in obesity.
 ...
PMID:Is obesity an inflammatory condition? 1174 55

Leptin is synthesized in adipocytes and acts primarily through central pathways suppressing appetite and increasing the metabolic rate in rodents as well as in humans. Recently leptin has also been suggested to have peripheral effects and be involved in insulin action. Since cytokines and chemokines may have effects on appetite regulation as well as on some of the obesity-related complications e.g. insulin resistance and cardiovascular disease, we investigated the effects of various cytokines and chemokines on leptin production in human adipose tissue fragments in vitro. Abdominal subcutaneous adipose tissue from healthy normal to overweight females was incubated for up to 48 h with the cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) and the chemokine: interleukin-8 (IL-8). IL-1beta (50 ng/ml) and TNF-alpha (10 ng/ml) decreased leptin production by 30-50% (P<0.05) and gene expression by 80-90% (P<0.05). In contrast, IL-6 and IL-8 had no effect on either leptin production or leptin gene expression. Interestingly, IL-1beta elicited a biphasic effect on leptin release with an incremental phase observed within 4 h with no concomitant change in leptin gene expression, followed by a long-lasting inhibition of leptin release and leptin gene expression. This could suggest that IL-1beta through a post-translational pathway induced an acute increase in leptin-secretion, perhaps through the release of leptin from a pre-formed pool within the adipose tissue. The long-term decrease in both leptin secretion and transcription could indicate that pro-inflammatory cytokines such as IL-1beta and TNF-alpha might influence the circulating leptin levels and thereby influence the adipose tissue to brain signalling, which could be of importance in relation to the obesity-associated diseases such as insulin resistance and cardiovascular disease.
 ...
PMID:Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. 1199 82

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.
 ...
PMID:Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. 1282 59

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
 ...
PMID:Obesity as a cardiovascular risk factor. 1467 64

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.
 ...
PMID:Analysis of candidate genes in Polish families with obesity. 1520 83

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.
 ...
PMID:Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity. 1537 81

Nearly half of the U.S. adult population is overweight or obese, which may be related to increased energy intake combined with lack of physical activity. Obesity increases the risk of several chronic diseases including diabetes, coronary heart disease, hypertension, and stroke. Conjugated linoleic acids (CLA) were shown to decrease fat and increase lean mass in several animal studies. However, the effects of CLA in combination with exercise (Ex) on body composition have not been studied in an animal model. We examined the effect of a low concentration of either safflower oil as control (0.5%) or mixed isomers of CLA (0.4%) along with treadmill exercise on body composition in male Balb/C mice fed a high-fat diet (20% corn oil) in a 2 x 2 factorial design. CLA consumption lowered change in fat mass (P < 0.001) confirming the results of other studies, and change in fat mass decreased further (P < 0.001) with CLA and exercise. Change in lean mass did not increase with exercise alone; it increased, although not significantly, with CLA alone and increased significantly (P < 0.05) due to the combination of CLA and exercise. This effect was accompanied by decreased serum leptin levels and lower leptin mRNA expression in peritoneal fat (P < 0.001). Serum insulin, glucose, tumor necrosis factor (TNF)-alpha, and interleukin-6 were lower in CLA-fed mice than in controls (P < 0.05), whereas serum TNF-alpha was increased by exercise (P < 0.05). Exercise increased oxygen consumption and energy expenditure when measured under resting conditions (P < 0.05). In summary, the combination of dietary CLA and exercise decreased fat mass and increased lean mass in mice fed a high-fat diet, and these effects may be related in part to decreased serum leptin and exercise-induced increases in oxygen consumption and energy expenditure.
 ...
PMID:The combination of dietary conjugated linoleic acid and treadmill exercise lowers gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C mice. 1586 92

Insulin resistance (IR) and obesity may be risk factors for breast cancer. The mechanism of IR in patients with cancer has not been fully clarified yet. This study was conducted to evaluate the possible role of circulating cytokines; tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in inducing IR in 20 overweight or obese patients with early stage breast cancer and to compare their levels with that of body mass index matched 20 healthy controls. IR was calculated by homeostasis model assessment (HOMA) method. Four groups were formed according to a 2.7 HOMA-IR cut-off value as breast cancer with or without IR and controls with or without IR. IL-6 and HOMA-IR values were found to be higher in breast cancer patients with IR compared to other groups. There was no significant difference in TNF-alpha levels between groups. HOMA-IR values correlated with estradiol and IL-6 levels in all breast cancer patients but not TNF-alpha. HOMA-IR values, serum insulin, estradiol and IL-6 levels in the receptor positive group were significantly higher than those of the receptor negative group. These results suggested a possible contribution of endogenous IL-6 production and hyperinsulinemia to the development of breast cancer in overweight or obese patients with prominent IR.
 ...
PMID:Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer. 1595 9

It is increasingly recognized that obstructive sleep apnea (OSA) syndrome is a systematic rather than local disorder. There is also growing evidence that apart from the syndrome's major features: intermittent hypoxia and sleep fragmentation, functional activity of the immune system is altered in OSA patients, with several cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) taking active part in sleep regulation. Little is known about the effects exerted by chronic intermittent hypoxia combined with persistent pro-inflammatory activity of the immune system on the vascular micro milieu in OSA. In this study we attempted to confirm the hypothesized imbalance between pro- and anti-angiogenic factors by evaluating direct and indirect angiogenic activity of OSA patients' sera in the in vivo serum-induced angiogenesis (SIA) and leukocyte-induced (LIA) assays, respectively, in mice. Both tests revealed significantly inhibited angiogenic activity of OSA patients' sera compared with healthy controls (P<0.001). Moreover, differences related to the subject's weight regarding in the mean number of newly-formed vessels were observed with a significantly greater inhibition in the normal-weighing apneic subjects than in the overweight or obese ones (P<0.01). The angiogenesis inhibition index was positively related to the serum IL-6 level (r=0.35; P<0.05) in the OSA group, but not to TNF-alpha, fasting serum leptin, or OSA syndrome severity as assessed by the AHI index. Our results demonstrate that OSA is accompanied by disturbed serum angiogenic activity, apparently resulting from an imbalance between pro- and anti-angiogenic factors, some of them being produced by the adipose tissue. The disordered angiogenic activity might be related to the pathophysiology of OSA and should be considered an important causative factor for the increased prevalence of cardiovascular diseases in OSA patients.
 ...
PMID:Disturbed angiogenic activity in sera from obstructive sleep apnea patients. 1620 78


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