Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Prader-Willi syndrome (PWS) is a well-defined syndrome of childhood-obesity which can serve as a model for investigating early onset childhood obesity. Many of the clinical features of PWS (e.g., hyperphagia, hypogonadotropic hypogonadism, growth hormone deficiency) are hypothesized to be due to abnormalities of the hypothalamus and/or pituitary gland. Children who become severely obese very early in life (i.e., before age 4 years) may also have a genetic etiology of their obesity, perhaps with associated neuroendocrine and hypothalamo-pituitary defects, as infants and very young children have limited access to environmental factors that contribute to obesity. We hypothesized that morphologic abnormalities of the pituitary gland would be seen in both individuals with PWS and other subjects with early onset morbid obesity (EMO). This case-control study included individuals with PWS (n = 27, age 3 months to 39 years), patients with EMO of unknown etiology (n = 16, age 4-22 years; defined as body mass index greater than the 97th centile for age before age 4 years), and normal weight siblings (n = 25, age 7 months to 43 years) from both groups. Participants had 3-dimensional magnetic resonance imaging to evaluate the pituitary gland, a complete history and physical examination, and measurement of basal pituitary hormones. Subjects with PWS and EMO had a higher prevalence of pituitary morphological abnormalities than did control subjects (74% PWS, 69% EMO, 8% controls; P < 0.001). Anterior pituitary hormone deficiencies were universal in individuals with PWS (low IGF-1 in 100%, P < 0.001 PWS vs. controls; central hypothyroidism in 19%, P = 0.052, and hypoplastic genitalia or hypogonadotropic hypogonadism in 100%, P < 0.001), and was often seen in individuals with EMO (6%, P = 0.89 vs. control, 31%, P = 0.002, and 25%, P = 0.018, respectively). The presence of a hypoplastic pituitary gland appeared to correlate with the presence of anterior pituitary hormone deficiencies in individuals with EMO, but no correlation was apparent in individuals with PWS. In conclusion, the high frequency of both morphological and hormonal abnormalities of the pituitary gland in both individuals with PWS and EMO suggests that abnormalities in the hypothalamo-pituitary axis are features not only of PWS, but also frequently of EMO of unknown etiology.
...
PMID:Pituitary abnormalities in Prader-Willi syndrome and early onset morbid obesity. 1743 97

IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men.
...
PMID:IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 1759 8

The imbalance in systemic mediators of inflammation, such as leptin, is thought to be involved in obesity-associated cancers. In addition, systemic endocrine signals can influence the local autocrine/paracrine factors produced within this microenvironment to influence epithelial cell fate. We previously demonstrated that leptin preferentially promotes the survival and proliferation of colon epithelial cells possessing an Apc mutation (IMCE) but not model normal cells (YAMC). Therefore, the purpose of this study was to identify leptin-induced functional gene family changes which characterize the response of colon epithelial cells possessing an Apc mutation but not normal cells. Consistent with our knowledge of colon carcinogenesis, genes regulating the Wnt/beta-catenin-mediated pathway including Mdm2, Pik3r1, and Rb1 were upregulated by leptin. Importantly, leptin induced IGF-mediated pathway gene expression changes and their protein products in IMCE cells. In the IMCE cells IGFBP-6, IGF-1, and Crim1 expression was upregulated, while IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and Nov expression was downregulated by leptin treatment. These data establish a biologically plausible mechanistic link between the elevated levels of growth factors and the increased risk of colon cancer associated with obesity.
...
PMID:Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashion. 1762 Mar 8

The prevalence of obesity, an established epidemiologic risk factor for many cancers, has risen steadily for the past several decades in the U.S. Particularly alarming are the increasing rates of obesity among children, portending continuing increases in the rates of obesity and obesity-related cancers for many years to come. Unfortunately, the mechanisms underlying the association between obesity and cancer are not well understood. In particular, the effects and mechanistic targets of interventions that modulate energy balance, such as reduced calorie diets and physical activity, on the carcinogenesis process have not been well characterized. The purpose of this review is to provide a strong foundation for future mechanistic-based research in this area by describing key animal and human studies of energy balance modulations involving diet, exercise, or pharmaceutical agents and by focusing on the interrelated pathways affected by alterations in energy balance. Particular attention in this review is placed on the components of the insulin/IGF-1/Akt pathway, which has emerged as a predominant target for disrupting the obesity-cancer link. Also discussed is the promise of global approaches, including genomics, proteomics, and metabolomics, for the elucidation of energy balance-responsive pathways. The ultimate goal of this work is to provide the missing mechanistic information necessary to identify targets for the prevention and control of cancers related to or caused by excess body weight.
...
PMID:Energy balance and carcinogenesis: underlying pathways and targets for intervention. 1769 8

In vertebrates and invertebrates, relationships between diet and health are controlled by a conserved signalling pathway responsive to insulin-like ligands. In invertebrate models for example, forkhead transcription factor family O (FOXO) transcription factors in this pathway regulate the rate of aging in response to dietary cues, and in vertebrates, obesity and age-induced deficits in the same pathway are thought to contribute to dysregulation of hepatic gluconeogenesis through genes such as phosphoenolpyruvate carboxykinase (PEPCK). Recently, we have begun to screen for dietary constituents capable of regulating this pathway in our cell culture model. Here, we identify three black tea theaflavins, theaflavin 3-O-gallate, theaflavin 3'-O-gallate, theaflavin 3,3'di-O-gallate and thearubigins as novel mimics of insulin/IGF-1 action on mammalian FOXO1a, PEPCK and moreover we provide evidence that the effects on this pathway of the green tea constituent (-)-epigallocatechin gallate depend on its ability to be converted into these larger structures. With the exception of water, tea is the most popular drink globally, but despite this, little is known about the biological availability of black tea polyphenols in vivo or the molecular target(s) mediating the effects presented here. Further investigation in these two areas might provide insight into how age-related metabolic disease may be deferred.
...
PMID:Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a. 1800 51

Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease.
...
PMID:Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease. 1805 18

Patients with adult growth hormone deficiency apparently can develop a clinical picture with pronounced obesity, dyslipidemia, decreased bone density, and increased fracture rate as well as psychosocial limitations irrespective of the loss and replacement of further hypophyseal axes. The extent of these changes is strongly dependent on interindividual variations. Retrospective analyses have indicated a possibility of elevated morbidity and mortality among this patient cohort which can be due to the proatherogenic alterations (central obesity, dyslipidemia). Treatment with recombinant growth hormone in controlled trials resulted in evident improvement in quality of life, better body composition and lipid profile as well as an increase in bone density. Whether these improvements will also pay off in terms of reduction of endpoints (decline in fracture rates, decrease of cardiovascular morbidity and mortality) has not yet been confirmed by controlled studies. When administered at low doses, titrated according to the IGF-1 level, growth hormone replacement appears to be a safe and well-tolerated therapeutic regimen.
...
PMID:[Growth hormone therapy in adults. Attempt to assess a decade of use]. 1841 67

Adiposity and adipocyte-derived cytokines have been implicated in prostate carcinogenesis. However, the relationship of adipokine gene variants with prostate cancer risk has not been thoroughly investigated. We therefore examined common variants of the IL6, LEP, LEPR, TNF and ADIPOQ genes in relation to prostate cancer in a case-control study nested within a large cohort of Finnish men. The study sample consisted of 1,053 cases of prostate cancer, diagnosed over an average 11 years of follow up, and 1,053 controls matched to the cases on age, intervention group and date of baseline blood draw. Logistic regression was used to model the relative odds of prostate cancer. We also examined genotypes in relation to serum insulin, IGF-1 and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (-14858A>G, -13973A>C, -13736C>A) in a potential regulatory region of the LEP gene conferred a statistically significant 20% reduced risk of prostate cancer. For example, at the -14858A>G locus, heterozygotes and homozygotes for the A allele had an odds ratio (OR) of prostate cancer of 0.76 [95% confidence interval (CI) 0.62, 0.93] and 0.79 (95% CI 0.60, 1.04), respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; 95% CI 0.99,1.67; p(trend) = 0.05). Polymorphisms in the IL6, LEPR, TNF and ADIPOQ genes were not associated with prostate cancer. Allelic variants in the LEP gene are related to prostate cancer risk, supporting a role for leptin in prostate carcinogenesis.
...
PMID:Adipokine genes and prostate cancer risk. 1903 56

Obesity, physical activity status and circulating levels of sex steroid hormones and growth factor proteins are intrinsically linked to energy balance. Epidemiological studies have previously reported associations between these factors and the risk of hormone-related cancers such as prostate and breast cancer in men and postmenopausal women. An increasing number of intervention studies in 'at-risk' populations and cancer survivors are now investigating the effects of lifestyle interventions that promote negative energy balance on circulating levels of sex hormones and growth factor proteins as surrogate markers of cancer risk. Evidence from these studies suggests that lifestyle interventions can improve insulin sensitivity, alter the balance of circulating sex steroid hormones and insulin-like growth factor (IGF) axis proteins (including IGF-1 and the IGF binding proteins 1 and 3) and change the functioning of immune cells in peripheral blood. Such changes could influence the risk of developing hormone-related cancers, as well as having the potential to improve disease-free survival in patients recovering from cancer treatment. However, despite promising results, the methodological quality of most intervention studies has been limited due to small subject numbers, lack of adequate control groups or non-randomised designs and the absence of long-term follow-up measures. More intervention studies with randomised controlled designs, higher numbers of subjects and longer-term follow-up measures are needed to establish which combination of specific dietary and physical activity interventions work best for reducing risk in 'at-risk' populations and survivors, optimal dose-response relationships and the magnitude of change in surrogate markers of cancer risk that is required to induce a protective effect.
...
PMID:Diet, physical activity and energy balance and their impact on breast and prostate cancers. 1907 86

Infection with Trypanosoma cruzi, the etiologic agent of Chagas disease is accompanied by an intense inflammatory reaction. Our laboratory group has identified adipose tissue as one of the major sites of inflammation during disease progression. Because adipose tissue is composed of many cell types, we were interested in investigating whether the adipocyte per se was a source of inflammatory mediators in this infection. Cultured adipocytes were infected with the Tulahuen strain of T. cruzi for 48-96 h. Immunoblot and quantitative PCR (qPCR) analyses demonstrated an increase in the expression of proinflammatory cytokines and chemokines, including interleukin (IL)-1 beta, interferon-gamma, tumor necrosis factor-alpha, CCL2, CCL5, and CXCL10 as well as an increase in the expression of Toll-like receptors-2 and 9 and activation of the notch pathway. Interestingly, caveolin-1 expression was reduced while cyclin D1 and extracellular signal-regulated kinase (ERK) expression was increased. The expression of PI3kinase and the activation of AKT (phosphorylated AKT) were increased suggesting that infection may induce components of the insulin/IGF-1 receptor cascade. There was an infection-associated decrease in adiponectin and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These data provide a mechanism for the increase in the inflammatory phenotype that occurs in T. cruzi-infected adipocytes. Overall, these data implicate the adipocyte as an important target of T. cruzi, and one which contributes significantly to the inflammatory response observed in Chagas disease.
Obesity (Silver Spring) 2008 Sep
PMID:Trypanosoma cruzi infection of cultured adipocytes results in an inflammatory phenotype. 1918 25


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

---