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

Obesity is a risk factor for colon cancer, possibly due to elevated levels of circulating cytokines derived from adipose tissue. Aspirin, which may affect the levels of these cytokines, has been shown in randomized controlled trials to decrease the risk of colorectal adenomas. We hypothesized that the chemopreventive effect of aspirin might be greater in individuals with higher body mass index (BMI). Data were available from the Aspirin/Folate Polyp Prevention Study, a randomized controlled trial of aspirin and folic acid to prevent recurrent colorectal adenomas. Obesity was defined as BMI > or = 30 (kg/m2), overweight as BMI of 25-29 (kg/m2) and normal weight as BMI <25 (kg/m2). For the analysis of the effect of aspirin on the recurrence of colorectal adenoma by BMI, we computed risk ratios for aspirin versus placebo within the three BMI strata using a modified Poisson model. Overall the risk reduction of adenomas with a daily dose of 325 mg aspirin was greater among subjects with higher BMI. Among obese subjects the risk ratio (RR) for advanced adenomas compared with placebo was 0.44 (95% CI 0.17-1.10), versus RR = 1.23 (95% CI 0.55-2.77) among those with normal weight. However, 81 mg aspirin daily did not interact with BMI to modify the risk of adenomas in such a fashion. The more pronounced effect of 325 mg aspirin in individuals with higher BMI suggests a possible protective role of anti-inflammatory aspirin against increased adipose-driven cytokines among obese subjects.
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PMID:Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States). 1711 Dec 62

While the fundamental metabolic function of calcium is to serve as a second messenger, coupling intracellular responses to extracellular signals, nutritional deficiency of calcium is manifested at a higher level of organization: 1) depletion of the calcium nutrient reserve; 2) inadequate complexation of digestive byproducts; and 3) collateral effects of hormones produced primarily to compensate for low calcium intake. The first mechanism contributes to the osteoporosis problem, the second to kidney stones and colon cancer, and the third to hypertension, preeclampsia, obesity, and insulin resistance, among others. Adequate calcium intakes (1000-1500 mg/d) in adults have been shown in controlled trials to lower the risk of osteoporotic fractures, kidney stones, obesity, and hypertension. The best source of calcium is dairy foods, largely because the disorders concerned depend upon multiple nutrients, not just calcium, and dairy provides a broad array of essential nutrients in addition to calcium, and at low cost.
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PMID:Calcium intake and disease prevention. 1711 94

Obesity, a risk factor for colon cancer, is associated with elevated serum levels of leptin, a protein produced by adipocytes. The aim of the present study was to clarify the effects of adipose tissue on colon cancer proliferation by using cultured cell lines. To achieve this, colon cancer cells (CACO-2, T84, and HT29) were cocultured with adipose tissue, isolated mature adipocytes, and isolated preadipocytes in a three-dimensional collagen gel culture system. The adipocytes and preadipocytes used were isolated from C57BL/6J and leptin-deficient ob/ob mice. Proliferation of the cancer cells was evaluated by nuclear bromodeoxyuridine uptake. The adipose tissue, mature adipocytes, and preadipocytes isolated from C57BL/6J mice significantly increased the proliferation of the colon cancer cells. This trophic effect of mature adipocytes on the cancer cell lines was observed only for cells from lean littermates and not for those from ob/ob mice. In contrast, the trophic effect of preadipocytes was not abolished in ob/ob mice, and this finding was supported by the result that leptin had a trophic effect on cancer cells. In conclusion, adipocytes were able to enhance the proliferation of colon cancer cells in vitro, partly via leptin, suggesting that adipose tissues, including mature adipocytes and preadipocytes, may promote the growth of colorectal cancer.
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PMID:Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. 1717 30

Seeds of Sinapis alba Linn. (commonly called yellow or white mustard) and their components have been reported to possess anticancer properties. In this study, we evaluated the efficacy of a novel mucilaginous fraction of mustard seeds in inhibiting colonic preneoplastic changes in animal models of sporadic and obesity-associated colon cancer. In two separate studies, male Sprague-Dawley or female Zucker obese rats, injected with azoxymethane (15 or 10 mg/kg body wt. once a week for 2 weeks, respectively), were fed AIN-93G diets with or without 5% mustard mucilage (MM) (w/w) for 8 weeks. Our aim was to measure the ability to modulate the number of aberrant crypt foci (ACF), putative preneoplastic lesions of the colon. The data were classified into total numbers of ACF and large ACF (crypt multiplicity of 4 or more). We report here that 5% MM significantly (p<0.05) decreased the number of total (approximately 21% inhibition) and large (approximately 50% inhibition) ACF in the colons of Sprague-Dawley rats compared to that in untreated controls. In addition, 5% MM supplemented diet significantly lowered (p<0.05) the number of total (approximately 63% inhibition) and large (approximately 60% inhibition) colonic ACF in Zucker obese rats compared to untreated obese rats, and had no effect on fasting plasma cholesterol or triglyceride levels. These results demonstrate the possible role of MM as a functional food against sporadic and obesity-associated colon cancer, and provide impetus to conduct research to understand the underlying mechanism(s) of action.
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PMID:Novel mucilage fraction of Sinapis alba L. (mustard) reduces azoxymethane-induced colonic aberrant crypt foci formation in F344 and Zucker obese rats. 1718 81

The physical inactivity and obesity involved in hyperglycemia and hyperinsulinemia is supposed to lead to an increased bioavailability of insulin-like growth factor-I (IGF-I). The carcinogenic effect of IGF-I may be influenced by IGF binding proteins. We investigated the association between plasma levels of C-peptide, a surrogate biomarker of insulin, IGFBP-1, IGF-I or IGFBP-3, and the risk of colorectal cancer in a nested case-control study. During an 11.5-year follow-up, 375 newly diagnosed colorectal cancers were identified in a cohort of 38,373 adults who had returned the baseline questionnaire and provided blood samples. Two matched-controls for each case were selected from the cohort. The odds ratio (OR) of colorectal cancer for plasma levels of each protein was estimated using the conditional logistic regression model adjusted for potential confounding factors. We observed a statistically significant association of plasma C-peptide with colorectal cancer only in men. The ORs were 1.0, 2.3, 2.8 and 3.2 along with quartiles (p trend, 0.0072). The association was stronger in colon cancer (p trend, 0.025) than in rectal cancer (p trend, 0.24). Other peptides were not associated with the risk in either men or women. The results did not change when repeatedly analyzed by tumor invasion levels, tumor sites or follow-up periods. In conclusion, a higher plasma C-peptide may indicate a subsequent risk of colorectal cancer in Japanese men.
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PMID:Plasma C-peptide, insulin-like growth factor-I, insulin-like growth factor binding proteins and risk of colorectal cancer in a nested case-control study: the Japan public health center-based prospective study. 1726 31

Obesity increases the risk of colon cancer. Hyperleptinemia is characteristic of obesity and leptin has been reported to be a colonic growth factor. We have examined the involvement of the cyclo-oxygenase (COX) pathways in the proliferation and anti-apoptotic effects of leptin. Leptin stimulated proliferation in HT-29 colon cancer cells: this was unaffected by inhibition of COX-1, COX-2, protein kinase C, or the epidermal growth factor receptor. Leptin did not increase COX-2 mRNA or COX-derived prostaglandin E2 production. Celecoxib induced apoptosis in a COX-independent manner. Leptin reduced both serum starvation- and celecoxib-induced apoptosis. Inhibition of ERK, p38 MAP kinase, and nuclear factor (NF)-kappaB abolished the growth-promoting and anti-apoptotic effects of leptin. Treatment of HT-29 cells with leptin stimulated phosphorylation of ERK and p38 MAP kinase and nuclear translocation of active NF-kappaB. We conclude that leptin stimulates colon cancer proliferation via COX-independent pathways and reduces celecoxib-induced apoptosis via ERK, p38 MAP kinase, and NF-kappaB pathways.
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PMID:Cyclo-oxygenase-independent inhibition of apoptosis and stimulation of proliferation by leptin in human colon cancer cells. 1740 16

Obesity and its related diseases are the leading cause of death in western society, with associated risks of hypertension, coronary heart disease, stroke, diabetes, and breast, prostate and colon cancer. Recent epidemiologic data indicate an increased risk of Alzheimer's disease in association with adult obesity. There is now convincing evidence that, in both human and animal models, the in utero environment may impact on fetal developmental processes, altering offspring homeostatic regulatory mechanisms. "Gestational programming" may result in altered cell number, organ structure, hormonal set points or gene expression, with effects being permanent or expressed only at select offspring ages (e.g., newborn, adult). Our laboratory and others have demonstrated that low birth weight rats, induced by maternal food restriction or uterine artery ligation, paradoxically develop adult obesity with glucose intolerance and hypertension. Recent studies indicate alterations in peripheral (hepatic) and central (hippocampus) IGF-1 gene expression and epigenetic regulation among these offspring. These findings suggest that potential risk factors for the development of Alzheimer's disease may be present as early as newborn life.
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PMID:Gestational programming of offspring obesity: a potential contributor to Alzheimer's disease. 1743 Feb 49

Recent evidence indicates that obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers, including those of the colon, prostate, and pancreas. Obesity, physical inactivity, visceral adiposity, hyperglycemia, and hyperinsulinemia are relatively consistent risk factors for colon cancer and adenoma. Also, patients with type 2 diabetes mellitus have a higher risk of colon cancer. For prostate cancer, the relationship to obesity appears more complex. Obesity seems to contribute to a greater risk of aggressive or fatal prostate cancer but perhaps to a lower risk of nonaggressive prostate cancer. Furthermore, men with type 2 diabetes mellitus are at lower risk of developing prostate cancer. Long-standing type 2 diabetes increases the risk of pancreatic cancer by approximately 50%. Furthermore, over the past 6 years, a large number of cohort studies have reported positive associations between obesity and pancreatic cancer. Together with data from prediagnostic blood specimens showing positive associations between glucose levels and pancreatic cancer up to 25 years later, sufficient evidence now supports a strong role for diabetes and obesity in pancreatic cancer etiology. The mechanisms for these associations, however, remain speculative and deserve further study. Hyperinsulinemia may be important, but the role of oxidative stress initiated by hyperglycemia also deserves further attention.
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PMID:The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. 1749 13

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.
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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

Obesity is a major public health problem associated with a wide range of health problems. This study estimates the prevalence of obesity, calculates the proportion (or population-attributable fraction [PAF]) of major chronic diseases which is attributable to obesity, estimates the deaths attributable to it and projects its future prevalence trends. In Canada, the overall age-standardized prevalence proportion of obesity has increased from 10 percent in 1970 to 23% in 2004 (8 percent to 23 percent in men and 13 percent to 22 percent in women). The increasing prevalence of obesity was observed for all five age groups examined: 20-34, 35-44, 45-54, 55-64 and 65+. On average, the PAF of prevalence of selected major chronic diseases which is attributable to obesity from 1970 to 2004 has increased by 138 percent for men and by 60 percent for women. Overall, in 2004, 45 percent of hypertension, 39 percent of type II diabetes, 35 percent of gallbladder disease, 23 percent of coronary artery diseases (CAD), 19 percent of osteoarthritis, 11 percent of stroke, 22 percent of endometrial cancer, 12 percent of postmenopausal breast cancer, and 10 percent of colon cancer could be attributed to obesity. In 2004, 8,414 (95 percent CI: 6,881-9,927) deaths were attributable to obesity. If current obesity prevalence trends remain unchanged, the prevalence proportion of obesity in Canada is projected to reach 27 percent in men and 24 percent in women by the year 2010. These increases will have a profound impact on the treatment needs and prevalence of a wide variety of chronic diseases, and also on the health care system in terms of capacity issues and resource allocation.
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PMID:The burden of adult obesity in Canada. 1762 59


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