UMLS:C0028754 - FACTA Search

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Query: UMLS:C0028754 (obesity)
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The levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) peak in human in their twenties, then decrease gradually with age. The physiological importance of DHEA was not clear until recent research reports showing that DHEA has beneficial effects on preventing diabetes, malignancy, inflammation, osteoporosis, and collagen disease. We summarize our results concerning diabetes, hepatitis, and colon cancer. In 1982, Coleman et al. [Diabetes 31 (1982) 830] reported that DHEA decreased hyperglycemia in diabetic db/db mice, which become insulin resistant. We measured hepatic gluconeogenic enzymes in an attempt to elucidate the mechanical mechanism of DHEA action. The activity and gene expression of hepatic gluconeogenic enzyme such as glucose-6-phosphatase (G6Pase) was increased in db/db mice despite hyperinsulinemia compared to control db/+m mice. DHEA, like troglitazone, decreased these levels in db/db mice. We also showed that DHEA improved the insulin resistance caused by aging or obesity using the glucose clamp technique in another animal model. In humans, the serum DHEA concentration was shown to be associated with hyperinsulinemia in diabetes. It also became clear that DHEA increased insulin secretion in old-aged db/db mice. DHEA increases not only insulin sensitivity due to the effects in the liver and muscle, but also insulin secretion. As an effect of DHEA on T-cell mediated hepatitis induced by concanavalin A (ConA), DHEA reduced hepatic injury by inhibiting several inflammatory mediators and apoptosis. As an effect of DHEA on carcinogenesis, DHEA would be a potential chemopreventative agent against colon cancer because it decreases the number of azoxymethane (AOM) induced aberrant crypt foci, which is a possible precursor to adenoma and cancer in a murine model.Thus, since DHEA has many beneficial effects experimentally, we should consider administration of DHEA in the future, and common mechanisms among these actions of DHEA should be elucidated in further studies.
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PMID:Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone. 1294 37

We used the nation-wide Swedish Family-Cancer Database to analyse cancer risks in men who had had children with more than one woman. Cancer cases were retrieved from the Swedish Cancer Registry from years 1961-1998. A total of 2.9 million men and 298,134 cancer cases were covered. For men having children with two, three or more women, increasing risk trends were shown for upper aerodigestive tract, lung, urinary bladder and oesophageal cancers. Decreasing trends were observed for tumours of the colon, skin (squamous cell and melanoma), nervous system and endocrine glands and against myeloma and non-Hodgkin's lymphoma. The present results indicated that men who had had children with multiple women showed an excess of smoking- and alcohol consumption-related cancers. The decreased risks for colon cancer, non-Hodgkin's lymphoma and melanoma were possibly related to lifestyle factors connected with economic deprivation, less obesity and physical fitness. These ill-defined protected factors may be a challenge to epidemiological studies.
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PMID:Cancer risks in men who had children with different partners from the Swedish Family-Cancer Database. 1451 98

Obesity is associated with an increased risk of colorectal cancer. Circulating levels of leptin are high in obesity and strongly correlated to levels of insulin. Leptin stimulates growth of colon cancer cells. In a nested case-control study, we measured leptin levels in prediagnostic plasma from 75 men and 93 women who were diagnosed with colorectal cancer mean time 3.4 years (SD 2.4) after recruitment and among 327 control subjects. Logistic regression analyses showed increases in colorectal cancer risk in men with increasing levels of leptin, odds ratios (OR) were 1.00 (ref), 0.85 (95% C.I.=0.33-2.23), 1.04 (0.43-2.53), and 2.15 (0.89-5.22), (pfor trend=0.08). There was a distinct threshold between the third and fourth quartile of leptin, and the odds ratio for top quartile vs. three bottom quartiles was 2.28 (1.09-4.76). Adjustment for body mass index and insulin did not affect risk estimates. In separate analysis, odds ratio for top vs. bottom tertile of colon cancer was 1.96 (95% C.I.=0.72-5.29), whereas no increase was seen for rectal cancer. In women, no association between leptin and risk was seen. These data support the hypothesis that leptin is a risk marker for colorectal cancer in men, but not in women.
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PMID:Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. 1453 36

Several epidemiological studies have supported the concept that high energy intake, obesity, and/or hyperinsulinemia are risk factors for colon cancer. Previously, it was shown that Zucker obese rats are more sensitive to chemically induced colon cancer than their lean counterparts. The present study investigated whether moderate (20-25%) dietary energy restriction (ER) would attenuate colon carcinogenesis in the Zucker obese rat model. Six-week-old Zucker obese (fa/fa) rats and lean (Fa/Fa) rats received s.c. injections of azoxymethane at a dose of 10 mg/kg body weight once weekly for 2 weeks. A week later, obese rats (n = 16) were assigned to an ER diet (Ob-ER group), based on a low-fat AIN-93G semisynthetic diet. The remaining obese and lean rats (n = 16 rats/group) were fed the low-fat diet ad libitum (Ob group and Ln group, respectively). All rats were euthanized after 8 weeks, and their colons were assessed for aberrant crypt foci (ACF; n = 8/group) or for the expression of transforming growth factor (TGF)-beta and cyclooxygenase (COX) isoforms at the protein and mRNA transcript levels (n = 8/group). Ob rats had a higher number of advanced ACF (crypt multiplicity >or=7) than Ln rats. Dietary ER significantly reduced the appearance of advanced ACF in Ob-ER rats without significantly affecting the blood insulin level or body weights. TGF-beta and COX isoforms were differentially expressed in the colonic mucosae of Ob and Ln rats. Dietary ER significantly reduced TGF-beta1/beta2 and COX-1/2 protein expression in obese rats. This study is the first to demonstrate that moderate ER attenuated TGF-beta and COX protein expression and the carcinogenic process in Zucker obese rats. These findings provide insights leading to the proposal that the mechanism(s) underlying the early events of colon carcinogenesis in Zucker obese rats may extend beyond the role of excessive body weight and hyperinsulinemia per se.
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PMID:Energy restriction reduces the number of advanced aberrant crypt foci and attenuates the expression of colonic transforming growth factor beta and cyclooxygenase isoforms in Zucker obese (fa/fa) rats. 1458 51

Epidemiological studies have shown that obesity and diabetes mellitus may be risk factors for colon cancer. However, the underlying mechanisms of how these chronic diseases promote colon carcinogenesis remain unknown. C57BL/KsJ-db/db mice have obese and diabetic phenotypes because of disruption of the leptin receptor. The present study was designed to investigate whether development of azoxymethane (AOM)-induced dysplastic and early neoplastic (premalignant) lesions of the colon is modulated in db/db mice. Homozygous db/db mice, heterozygous db/+ mice and littermate controls (+/+) were injected with AOM under food restriction ( approximately 10.8 kcal/mouse/day) and killed 5 weeks after the carcinogen treatment. Their colons were assessed for premalignant lesions induced by AOM. We found a significant increase in the multiplicity of the total premalignant lesions in db/db mice when compared with db/+ or +/+ mice. Phenotypically, serum leptin and insulin levels in db/db mice were significantly higher than those in db/+ or +/+ mice, whereas the body weights and glucose levels in blood of db/db, db/+ and +/+ mice were comparable. In addition, immunostaining of the leptin receptor and insulin-like growth factor-I receptor showed up-regulation of these protein levels specifically in the lesions. Our data indicate that development of AOM-induced premalignant lesions is enhanced in db/db mice with hyperleptinemia and hyperinsulinemia. The results have important implications for further exploration of the possible underlying events that affect the positive association between colon cancer and chronic diseases (obesity and diabetes).
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PMID:Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. 1472 96

Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.
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PMID:Obesity and colon cancer: does leptin provide a link? 1473 82

Physical activity has been shown to reduce risk of colon cancer. Some studies have shown site-specific associations while others have not. The inverse association between physical activity and colon cancer is consistent although only 7 of 13 studies that have collected both colon and rectal cancer data in the same manner report reduced risk for rectal cancer; four of these studies detected statistically significant inverse associations. The frequency, duration and intensity of activity are important components of a public health message to reduce risk of colon cancer through performance of physical activity. However, difficulties in estimating the exact amount of activity needed and frequency and intensity of activity result in only crude estimates of dose needed for a protective effect. Much of the literature suggest that more intense activity is needed to reduce colon cancer risk and that somewhere between 3.5 and 4 hours of vigorous activity per week may be needed to optimise protection. Several biological mechanisms have been proposed to explain the association between physical activity and colon cancer; many of these mechanisms also support the observation that intense activities are most protective. Biological mechanisms include: physical activity increasing gut motility; enhancing the immune system; decreasing insulin and insulin-like growth factor levels; decreasing obesity; enhancing free radical scavenger systems; and influencing prostaglandin levels. The evidence taken together provides strong support for lack of physical activity being causally related to colon cancer. It has been estimated that 12-14% of colon cancer could be attributed to lack of frequent involvement in vigorous physical activity.
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PMID:Physical activity and colorectal cancer. 1504 16

Regular physical activity provides health benefits, including the reduction in risks of coronary heart disease, hypertension, type 2 diabetes mellitus, obesity, colon cancer, and premature mortality. Despite this information, most women are physically inactive. Research findings shed light on the gender differences in physiological responses to physical activity. Patterns and predictors of physical activity vary significantly by gender. Further study is needed of the benefits, barriers, and personally meaningful outcomes of physical activity for women, specifically including the frequently unspoken correlates of urinary incontinence, depression and mood disorders, and obesity.
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PMID:Physical activity and exercise in women's health. 1506 35

Many of the cancers common in the Western world, including colon, prostate and breast cancers, are thought to relate to dietary habits. Of the known risk factors, many will act through increasing the probability of mutation. Recognised dietary mutagens include cooked meat compounds, N-nitroso compounds and fungal toxins, while high meat and saturated fat consumption, increasing rates of obesity, and regular consumption of alcohol and tobacco are all dietary trends that could indirectly enhance the probability of mutation. However, there are significant difficulties in implementing and sustaining major dietary changes necessary to reduce the population's intake of dietary mutagens. Dietary antimutagens may provide a means of slowing progression toward cancer, and be more acceptable to the population. Consideration of genetic mechanisms in cancer development suggest several distinct targets for intervention. Strategies that reduce mutagen uptake may be the most simple intervention, and the one least likely to result in undesirable side effects. Certain (but not all) types of dietary fibres appear to reduce mutation through this mechanism, as may certain probiotics and large planar molecules such as chlorophyllin. Antioxidants have been suggested to scavenge free radicals, and prevent their interactions with cellular DNA. Small molecule dietary antioxidants include ascorbic acid, Vitamin E, glutathione, various polyphenols and carotenoids. We found a statistically significant relationship between colon cancer incidence and soil selenium status across different regions of New Zealand. Additionally, a study of middle-aged men suggested that blood selenium levels lower than 100 ng/ml were inadequate for repair or surveillance of oxidative (and other) DNA damage. We suggest that selenium will be an important antimutagen, at least in New Zealand, possibly through antioxidant effects associated with selenium's role in enzymes associated with endogenous repair of DNA damage. Modulation of xenobiotic metabolizing enzymes is well recognised as cancer-protective, and is a property of various flavonoids and a number of sulfur-containing compounds. Many fruits and vegetables contain compounds that will protect against mutation and cancer by several mechanisms. For example, kiwifruit has antioxidant effects and may also affect DNA repair enzymes. Dietary folate may be a key factor in maintenance of methylation status, while enhanced overall levels of vitamins and minerals may retard the development of genomic instability. The combination of each of these factors could provide a sustainable intervention that might usefully delay the development of cancer in New Zealand and other populations. Although there are a range of potentially antimutagenic fruits, vegetables and cereals available to these populations, current intake is generally below the level necessary to protect from dietary or endogenous mutagens. Dietary supplementation may provide an alternative approach.
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PMID:Dietary cancer and prevention using antimutagens. 1513 38

The incidence of colon cancer is high in many developed nations, especially New Zealand. Molecular understanding of the nature of colon cancer shows a disease whose well-characterized morphological progression is paralleled at the cellular level by increased numbers of gene or chromosome mutations, loss of heterozygosity, changed methylation patterns, and genomic instability. In the present study, we consider whether an imbalance of factors that affect DNA methylation patterns might explain at least part of the high colon cancer incidence in New Zealand. Folate is the major micronutrient whose intake impacts methylation, particularly through interaction with choline and methionine. Folate is generally somewhat deficient in the New Zealand diet, with the voluntary addition of folate to white flour not producing desired levels. Selenium affects methylation status in several ways and is recognized as being low in New Zealand soils and, therefore, diet. Zinc is also low in the diets of some New Zealand population groups, which can lead to hypomethylation. Several of the components of fruits and vegetables affect methylation patterns, and the average New Zealand intake, at two to three servings per day, is considerably below recommended amounts. Low dietary fiber, high tobacco use, and increasing rates of obesity are also likely New Zealand risk factors that may impact on methylation status. Dietary supplementation is not as common in New Zealand as in countries such as the United States, but may provide a way to raise the levels of nutrients and phytochemicals affecting methylation status, thereby enhancing colon cancer protection.
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PMID:Epigenetic events and protection from colon cancer in New Zealand. 1519 45

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