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

Casitas b-lineage lymphoma (c-Cbl) is a multiadaptor protein with E3-ubiquitin ligase activity involved in regulating the degradation of receptor tyrosine kinases. We have recently reported that c-Cbl(-/-) mice exhibit a lean phenotype and enhanced peripheral insulin action likely due to elevated energy expenditure. In the study reported here, we examined the effect of a high-fat diet on energy homeostasis and glucose metabolism in these animals. When c-Cbl(-/-) mice were fed a high-fat diet for 4 weeks, they maintained hyperphagia, higher whole-body oxygen consumption (27%), and greater activity (threefold) compared with wild-type animals fed the same diet. In addition, the activity of several enzymes involved in mitochondrial fat oxidation and the phosphorylation of acetyl CoA carboxylase was significantly increased in muscle of high-fat-fed c-Cbl-deficient mice, indicating a greater capacity for fat oxidation in these animals. As a result of these differences, fat-fed c-Cbl(-/-) mice were 30% leaner than wild-type animals and were protected against high-fat diet-induced insulin resistance. These studies are consistent with a role for c-Cbl in regulating nutrient partitioning in skeletal muscle and emphasize the potential of c-Cbl as a therapeutic target in the treatment of obesity and type 2 diabetes.
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PMID:Casitas b-lineage lymphoma-deficient mice are protected against high-fat diet-induced obesity and insulin resistance. 1650 34

High-dose therapy with autologous hematopoietic cell transplantation (auto-HCT) is frequently used to improve outcomes in lymphoma. However, small studies suggest a survival disadvantage among obese patients. Using a retrospective cohort analysis, we studied the outcomes of 4681 patients undergoing auto-HCT for Hodgkin or non-Hodgkin lymphoma between 1990 and 2000 according to body mass index (BMI). Four groups categorized by BMI were compared by using Cox proportional hazards regression to adjust for other prognostic factors. A total of 1909 patients were categorized as normal weight (BMI 18-25 kg/m2), 121 as underweight (BMI<18 kg/m2), 1725 as overweight (BMI>25-30 kg/m2), and 926 as obese (BMI>30 kg/m2) at the time of HCT. Outcomes evaluated included overall survival, relapse, transplantation-related mortality (TRM), and lymphoma-free survival. TRM was similar among the normal, overweight, and obese groups; the underweight group had a higher risk of TRM (relative risk [RR], 2.46; 95% confidence interval [CI], 1.59-3.82; P<0.0001) compared with the normal-BMI group. No differences in relapse were noted. Overall mortality was higher in the underweight group (RR, 1.48; 95% CI, 1.17-1.88; P=.001) and lower in the overweight (RR, 0.87; 95% CI, 0.79-0.96; P=.004) and obese (RR, 0.76; 95% CI, 0.67-0.86; P<.0001) groups compared with the normal-BMI group. In light of our inability to find differences in survival among overweight, obese, and normal-weight patients, obesity alone should not be viewed as a contraindication to proceeding with auto-HCT for lymphoma when it is otherwise indicated.
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PMID:Effect of body mass index on mortality of patients with lymphoma undergoing autologous hematopoietic cell transplantation. 1663 89

Casitas b-lineage lymphoma (c-Cbl) is a multiadaptor protein with E3-ubiquitin ligase activity residing within its RING finger domain. We have previously reported that c-Cbl-deficient mice exhibit elevated energy expenditure, reduced adiposity, and improved insulin action. In this study, we examined mice expressing c-Cbl protein with a loss-of-function mutation within the RING finger domain (c-Cbl(A/-) mice). Compared with control animals, c-Cbl(A/-) mice display a phenotype that includes reduced adiposity, despite greater food intake; reduced circulating insulin, leptin, and triglyceride levels; and improved glucose tolerance. c-Cbl(A/-) mice also display elevated oxygen consumption (13%) and are protected against high-fat diet-induced obesity and insulin resistance. Unlike c-Cbl(A/-) mice, mice expressing a mutant c-Cbl with the phosphatidylinositol (PI) 3-kinase binding domain ablated (c-Cbl(F/F) mice) exhibited an insulin sensitivity, body composition, and energy expenditure similar to that of wild-type animals. These results indicate that c-Cbl ubiquitin ligase activity, but not c-Cbl-dependent activation of PI 3-kinase, plays a key role in the regulation of whole-body energy metabolism.
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PMID:Genetic ablation of the c-Cbl ubiquitin ligase domain results in increased energy expenditure and improved insulin action. 1713 Apr 87

The incidence of non-Hodgkin's lymphoma (NHL) has risen dramatically over recent decades and, despite some known risk factors, such as compromised immunity, the etiology of NHL and the reasons for most of this increase are unknown. Dietary components may be a common and critical source of immunologic antigens and promoters, which needs to be incorporated more in the etiologic research of NHL. To date, epidemiologic evidence suggests that obesity and fat intake, in particular saturated or animal fat, may increase the risk of NHL; whereas whole-grains, vegetables and moderate consumption of alcohol may be inversely associated with NHL risk. Much of the current evidence is obtained from case-control studies, which are subject to dietary recall bias; therefore, this area of research requires further study within prospective cohorts with detailed dietary information and with a large number of cases to examine disease sub-type heterogeneity.
Leuk Lymphoma 2006 Dec
PMID:The role of dietary factors in the epidemiology of non-Hodgkin's lymphoma. 1716 93

Non-Hodgkin lymphoma (NHL) represents a group of heterogeneous diseases that significantly vary in their causes, molecular profiles, and natural progression. In 2007, there will be approximately 59,000 newly diagnosed NHL cases in the United States and over 300,000 cases worldwide. Although new therapeutic regimens are minimizing the number of deaths related to NHL, causes for the majority of lymphomas remain undetermined. Recent studies suggest that dietary factors may contribute to the rising rates of NHL. This review will summarize epidemiologic reports that have studied the relationship between obesity, physical activity, and diet and risk of NHL. Based on a number of case-control and prospective cohort studies, overweight/obesity probably increases the risk of NHL, whereas moderate physical activity may reduce risk. Several studies support an inverse association between intakes of vegetables and NHL risk, particularly for the consumption of cruciferous vegetables. This may relate to the induction of apoptosis and growth arrest in preneoplastic and neoplastic cells, two important actions of isothiocyanates found in cruciferous vegetables. Studies also suggest that fish intake may be inversely associated with risk of NHL, although findings have not been entirely consistent. This may relate to the high organochlorine content in some fish that could override a protective effect. High consumption of fats, meat, and dairy products also may increase lymphoma risk. The accumulated scientific evidence concerning the associations between obesity, diet, and NHL suggests several identified modifiable risk factors that might be recommended to decrease lymphoma risk.
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PMID:Obesity, diet and risk of non-Hodgkin lymphoma. 1733 42

Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence, however, suggests that a decrease in circulating high-density lipoprotein cholesterol (HDL-C) may occur during lymphomagenesis, reflecting underlying etiology such as inflammation. We investigated the relationship between prediagnostic HDL-C and non-Hodgkin lymphoma (NHL) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. At baseline, serum HDL-C and total cholesterol concentrations from fasting blood, information on diet and lifestyle, and direct measurements of height, weight, and blood pressure were obtained from 27,074 healthy male smokers of ages 50 to 69 years. Cox proportional hazards models with age as underlying time metric was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). We found no association between total or non-HDL cholesterol and the 201 incident NHL cases ascertained during the follow-up (1985-2002), but observed an inverse association between HDL-C and NHL, which changed with length of follow-up. High HDL-C was associated with lower risk of all NHL during the first 10 years (n = 148; RR for 5th versus 1st quintile, 0.35; 95% CI, 0.19-0.62; P(trend) < 0.0001), but not with diagnoses during later follow-up (n = 53; RR, 1.31; 95% CI, 0.55-3.10). The inverse association was similar for NHL subtypes and was not modified by obesity, blood pressure, physical activity, or alcohol intake, but seemed to be stronger in men with lower duration of smoking (P(interaction) = 0.06). Our findings implicate HDL-C as a preclinical indicator of NHL and warrant further prospective investigations for its etiologic contribution.
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PMID:Serum high-density lipoprotein cholesterol and risk of non-hodgkin lymphoma. 1752 88

The classical view according to which overweight/obesity is related to cancer considers adipose tissue as an active and metabolic "organ", acting through endocrine, autocrine and paracrine processes. Consequently, it has been hypothesized, that genesis and progression of cancer may be caused by different biological factors acting through diverse mechanisms including changes in the synthesis and bioavailability of sex hormones, insulin resistance, release of growth factors and/or proinflammatory cytokines and abnormal energetic disposal and expenditure. We have shown that overweight/obesity can be experimentally induced by benzo[a]pyrene, a universal well characterized chemical pollutant and that overweight/obesity may in fact be caused by several types of chemical pollutants. In this paper we propose that in addition to the above hypothetical biological mechanisms, adipose tissue acts as a reservoir for lipophilic, liposoluble environmental carcinogens, so that chemical pollution may in fact generate both overweight/obesity and cancer. More precisely, we propose that many carcinogens, be they mutagens or promotors can be stored in the adipose tissue, be released at convenient dose in the blood circulation and therefore target peripheral tissues to induce carcinogenesis. Such carcinogens mainly include organochlorine pesticides and PCBs. Their association with an increased risk of cancer seems to be demonstrated for breast and prostate carcinoma, as well as for lymphoma, not only in obese patients, but also in normal weight or even leaner patients suggesting that the adipose tissue may act as a reservoir for environmental carcinogens in obese as well as in non-obese patients.
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PMID:Overweight/obesity and cancer genesis: more than a biological link. 1803 14

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.
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PMID:Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease. 1805 18

Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL, self-reported anthropometric data on weight and height from over 10,000 cases of NHL and 16,000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m(-2) or more, was not associated with NHL overall (pooled OR = 1.00, 95% confidence interval (CI) 0.70-1.41) or the majority of NHL subtypes. An excess was however observed for diffuse large B-cell lymphoma (pooled OR = 1.80, 95% CI 1.24-2.62), although not all study-specific ORs were raised. Among the overweight (BMI 25-29.9 kg m(-2)) and obese (BMI 30-39.9 kg m(-2)), associations were elevated in some studies and decreased in others, while no association was observed among the underweight (BMI < 18.5 kg m(-2)). There was little suggestion of increasing ORs for NHL or its subtypes with every 5 kg m(-2) rise in BMI above 18.5 kg m(-2). BMI components height and weight were also examined, and the tallest men, but not women, were at marginally increased risk (pooled OR = 1.19, 95% CI 1.06-1.34). In summary, whilst we conclude that there is no evidence to support the hypothesis that obesity is a determinant of all types of NHL combined, the association between severe obesity and diffuse large B-cell lymphoma may warrant further investigation.
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PMID:Non-Hodgkin lymphoma and obesity: a pooled analysis from the InterLymph Consortium. 1844 86

Companion animals represent an under-utilised resource. The present paper is designed to encourage collaborative studies. Dogs and cats are out-bred animals that are willing to consume a consistent diet for long periods, so are ideal candidates for prospective studies of naturally-occurring disease. In some studies the effect of diet on survival has been substantial. Food restriction, for example, slows the development of osteoarthritis and increases the lifespan of Labrador retrievers by 2 years, protein and P restriction more than doubles the median survival time of dogs and cats with chronic kidney disease and adding n-3 fats and arginine to the diet of dogs with stage 3 lymphoma improves median survival time by one-quarter. Obesity is also very common in both dogs and cats and is also associated with disease as in human subjects. When interpreting these results, however, it is essential to take into account pathophysiological differences among species. Dogs and cats do not display all the characteristics of metabolic disease in human subjects, they metabolise fat well and atherosclerosis and cardiac infarction are uncommon. Such differences should not, however, preclude further study because differences among species often clarify knowledge. Monitoring of disease in companion animals may also provide a surveillance system for the safety of the food supply, as illustrated by recent outbreaks of acute renal failure and liver failure in cats and dogs in the USA caused respectively by melamine and mycotoxin contamination of pet foods.
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PMID:Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Nutritional therapies to improve health: lessons from companion animals. 1904 Jul 82


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