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

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

Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be more common in women than in men. However, the interaction of gender and age has rarely been analyzed in detail, and knowledge of the distinction between pre- and postmenopausal women is lacking. Some of the studies that have described a higher prevalence of HF-NEF in women relied on clinical diagnoses of HF together with normal systolic function and did not measure diastolic function. This applies to the analysis of patients hospitalized for HF and some epidemiological investigations that agree on the greater prevalence of HF-NEF in women. Population-based studies with echocardiographic determination of diastolic function have suggested equal or greater prevalence of diastolic dysfunction in men. Major risk factors for HF-NEF include hypertension, aging, obesity, diabetes, and ischemia. Hypertension is more frequent in women and can contribute to left ventricular and arterial stiffening in a gender-specific way. Aging, obesity, and diabetes affect myocardial and vascular stiffness differently and lead to different forms of myocardial hypertrophy in women and men. In contrast, ischemia may play a greater role in men. Gender differences in ventricular diastolic distensibility, in vascular stiffness and ventricular/vascular coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms may contribute to a greater rate of HF-NEF in women. The underlying molecular mechanisms include gender differences in calcium handling, in the NO system, and in natriuretic peptides. Estrogen affects collagen synthesis and degradation and inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to premenopausal women, and the loss of its protective mechanisms may render the heart of postmenopausal women more vulnerable. Thus, a number of molecular mechanisms can contribute to the gender differences in HF-NEF.
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PMID:Role of gender in heart failure with normal left ventricular ejection fraction. 1718 12

Green tea catechins (GTCs) are polyphenolic flavonoids formerly called vitamin P. GTCs, especially (-)-epigallocatechin-3-gallate (EGCG), lower the incidence of cancers, collagen-induced arthritis, oxidative stress-induced neurodegenerative diseases, and streptozotocin-induced diabetes. Also, inhibition of adipogenesis by green tea and green tea extract has been demonstrated in cell lines, animal models, and humans. The obesity-preventive effects of green tea and its main constituent EGCG are widely supported by results from epidemiological, cell culture, animal, and clinical studies in the last decade. Studies with adipocyte cell lines and animal models have demonstrated that EGCG inhibits extracellular signal-related kinases (ERK), activates AMP-activated protein kinase (AMPK), modulates adipocyte marker proteins, and down-regulates lipogenic enzymes as well as other potential targets. Also, the catechin components of green tea have been shown to possess anti-carcinogenic properties possibly related to their anti-oxidant activity. In addition, it was shown that dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus. In this review, the biological activities and multiple mechanisms of EGCG in cell lines, animal models, and clinical observations are explained.
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PMID:Proposed mechanisms of (-)-epigallocatechin-3-gallate for anti-obesity. 1736 40

Obesity is an established risk factor for breast cancer incidence and mortality. However, the mechanism that links obesity to tumorigenesis is not well understood. Here we combined nonlinear optical imaging technologies with an early-onset diet-induced obesity breast cancer animal model to evaluate the impact of obesity on the composition of mammary gland and tumor stroma. Using coherent anti-Stokes Raman scattering and second harmonic generation on the same platform, we simultaneously imaged mammary adipocytes, blood capillaries, collagen fibrils, and tumor cells without any labeling. We observed that obesity increases the size of lipid droplets of adipocytes in mammary gland and collagen content in mammary tumor stroma, respectively. Such impacts of obesity on mammary gland and tumor stroma could not be analyzed using standard two-dimensional histologic evaluation. Given the importance of mammary stroma to the growth and migration of tumor cells, our observation provides the first imaging evidence that supports the relationship between obesity and breast cancer risk.
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PMID:Nonlinear optical imaging to evaluate the impact of obesity on mammary gland and tumor stroma. 1753 86

The skeleton is the most common site of metastasis in patients with advanced prostate cancer. Despite many advances in targeting skeletal metastases, the mechanisms behind the attraction of prostate cancer cells to the bone are not known. Osteoclast cathepsin K, due to its ability to effectively degrade bone matrix collagen I, has been implicated in colonization and growth of prostate tumours in the bone. Identification of new cathepsin K substrates in the bone microenvironment and the recent findings demonstrating its involvement in obesity and inflammation suggest additional roles for this enzyme in skeletal metastases of prostate cancer.
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PMID:Cathepsin K in the bone microenvironment: link between obesity and prostate cancer? 1763 27

Diabetes mellitus type 2 is a major factor for cardiovascular diseases. The toxic effects of chronic hyperglycemia involve many alterations in the vascular tissue, including atherosclerosis. The pathogenesis of atherosclerosis in the diabetic syndrome (DS-II) has not been fully elucidated. A better understanding of the progress of DS-II at the level of the aorta could help us to identify inhibitors of atherosclerosis. Studies have shown that obesity and high calorie diet (HCD) are associated with the development of DS-II, however the lack of naturally occurring experimental models of DS-II have impaired to directly address these issues. We hypothesize that a HCD induces DS-II. This study (15 months duration) is designed to determine if HCD induces DS-II in the desert sand rat (Psammomys obesus; P. obesus). We also evaluated the histopathology of the aorta in animals fed with a laboratory chow pellets ad libitum (hypercaloric) and in control (animals fed with the naturally occurring hypocaloric diet; halophile plants). The weight and blood chemistry (glucose, lipids, and insulin levels) were evaluated periodically (once per week), and the histology of the aortas of these animals were assessed every 3 months for up to 12 months, during the development of DS-II. This study demonstrates that 40% of the animals in HCD develop DS-II at 3 months. Histological characterization demonstrates the typical alterations observed in atherosclerosis, i.e., alteration of the elastic fibers of the media layer and enrichment in collagen and glucosaminoglycans. This study demonstrates that P. obesus is an excellent animal model to study the progression of DS-II and the development of atherosclerosis.
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PMID:A high calorie diet induces type 2 diabetes in the desert sand rat (Psammomys obesus). 1766 65

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.
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PMID:Fibrogenesis in fatty liver associated with obesity and diabetes mellitus type 2. 1784 88

Recent studies have added to the evidence that type 1 and type 2 diabetes are associated with increased risk of hip fracture and other fractures. More frequent falls probably account for some of this increased risk, but reduced bone strength may also play a role. Although type 1 diabetes is associated with lower bone density, those with type 2 diabetes usually have elevated bone density. Yet for both types of diabetes, bone appears to be more fragile for a given density. Diabetes can affect bone through multiple pathways-some with contradictory effects-including obesity, insulin levels, hyperglycemia, and advanced glycation end products in collagen. Treatment with thiazolidinediones may increase fracture risk, at least in older women. Clinicians need to be aware of the increased fracture risk associated with diabetes. Additional research is needed to clarify the mechanisms underlying this increased risk and the best approaches to fracture prevention.
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PMID:Diabetes, fracture, and bone fragility. 1792 91

Obesity is associated with asthma and airway hyperresponsiveness. Leptin modulates some of the proinflammatory effects observed in obesity. The objective of this study was to determine the effects of leptin on airway smooth muscle responses. The effect of leptin (0.1-100 ng/ml) on migration (toward platelet-derived growth factor [PDGF], 10 ng/ml, across collagen-coated membrane in Transwell culture plates), proliferation (by BrDU incorporation), and cytokine production (by Bioplex bead assay) of cultured human airway smooth muscle cells from nine nonasthmatic donors was assessed. Effects of leptin on the contractile responses were studied in bovine tracheal smooth muscle rings. Leptin receptor expression and activation of STAT-3, Src kinase, Suppressor of Cytokine Signaling-3 (SOCS-3), and COX were evaluated by Western blotting and PCR. PGE(2) levels in supernatant were assessed by enzyme immunoassay. Human airway smooth muscle cells express leptin receptor, which, when engaged, phosphorylated STAT-3. Leptin inhibited PDGF-induced human airway smooth muscle migration and proliferation and IL-13-induced eotaxin production. Leptin did not stimulate cytokine synthesis and did not evoke contractile responses or inhibit isoproterenol-induced relaxation of carbachol-induced contraction of bovine tracheal rings. The inhibitory effects on migration and eotaxin production are not due to activation of SOCS-3 but are partly due to increased production of PGE(2) because they were attenuated by indomethacin. In conclusion, leptin inhibited human airway smooth muscle proliferation, migration toward PDGF, and IL-13-induced eotaxin production. This is partly mediated by PGE(2) secretion from smooth muscle cells induced by leptin. The association between obesity and asthma is unlikely to be due to a direct effect of leptin on airway smooth muscle.
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PMID:The effects of leptin on airway smooth muscle responses. 1842 Oct 18

Prediabetes [impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG)] is a major risk factor for T2DM as well as for cardiovascular disease and mortality. In the present study, the platelet aggregation and fibrinogen levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidemia. Thirty-nine subjects with prediabetes (24 IFG and 15 IGT) and age, sex and BMI matched 36 healthy controls were enrolled. Platelet aggregation, fibrinogen and hsCRP levels, HOMA-IR and HOMA-beta indexes were determined. Platelet aggregation induced by collagen, epinephrine or ADP was not different (p=0.93, p=0.90 and p=0.29, respectively) between two groups, whereas fibrinogen levels were significantly higher (p=0.006) in the prediabetics when compared to controls. hsCRP levels, HOMA-IR and HOMA-beta indexes in the two groups were not different. The power of the study was calculated according to the results and established as 0.97 for collagen, 0.95 for epinephrine and 0.83 for ADP. Despite the high plasma fibrinogen levels, the platelet aggregation in prediabetics was not different when compared to healthy controls. These data suggest that platelet aggregation may not be involved in the mechanism of prothrombotic state in prediabetic state.
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PMID:Platelet aggregation is not enhanced in patients with prediabetes. 1848 75


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