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

We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited by intestinal luminal compounds that are inefficiently absorbed and naturally present in foods. Because of their abundance in fruits and vegetables, flavonoids were selected as model compounds. Robust inhibition of glucose and fructose transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its glucoside precursor isoquercitrin [corrected]. IC50s for quercetin, myricetin, and isoquercitirin [corrected]were approximately 200- to 1000-fold less than glucose or fructose concentrations, and noncompetitive inhibition was observed. The two other major intestinal sugar transporters, GLUT5 and SGLT1, were unaffected by flavonoids. Sugar transport by GLUT2 overexpressed in pituitary cells and naturally present in Caco-2E intestinal cells was similarly inhibited by quercetin. GLUT2 was detected on the apical side of Caco-2E cells, indicating that GLUT2 was in the correct orientation to be inhibited by luminal compounds. Quercetin itself was not transported by the three major intestinal glucose transporters. Because the flavonoid quercetin, a food component with an excellent pharmacology safety profile, might act as a potent luminal inhibitor of sugar absorption independent of its own transport, flavonols show promise as new pharmacologic agents in the obesity epidemic.
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PMID:Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. 1717 39

Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12-week diets of chow or chow plus candy. The latter were randomized for 12 further weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert to chow-only diet. Energy expenditure was measured, and oral glucose tolerance tests (OGTTs) were performed. Body composition was determined by dual-energy X-ray absorptiometry scanning, and pancreatic beta-cell mass was determined by histology. Candy feeding increased weight, fat mass, and feeding-associated energy expenditure. Liraglutide or reversal to chow diet fully reversed weight and fat gains. Liraglutide was associated with decreased calorie intake and shifted food preference (increased chow/decreased candy consumption). Despite weight loss, liraglutide-treated rats did not decrease energy expenditure compared with candy-fed controls. Vildagliptin affected neither weight, food intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly suggested that both drugs increased insulin sensitivity. Liraglutide and vildagliptin inhibited obesity-associated increases in beta-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of beta-cell to body mass was low.
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PMID:Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not. 1719 59

Clifton Leaf, in his article "Why We're Losing the War on Cancer," presents criticisms of past research approaches and the small impact of this research thus far on producing cures or substantially extending the life of many cancer patients. It is true that gains in long-term survival for people with advanced cancers have been modest, hindered in part by the heterogeneity of tumors, which allows the cancers to persist using alternate molecular pathways and so evade many cancer therapeutics. In contrast, clinical trials have demonstrated that it is possible to reduce the incidence or improve cancer survival through prevention and early detection. Strides have been made in preventing or detecting early the four deadliest cancers in the United States (i.e., lung, breast, prostate, and colorectal). For example, 7-year follow-up data from the Breast Cancer Prevention Trial (BCPT) provides evidence that tamoxifen reduces the occurrence of invasive breast tumors by more than 40%; recent studies using aromatase inhibitors and raloxifene are also promising. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride reduced prostate cancer incidence by 25%, and the ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT) is investigating selenium and vitamin E for prostate cancer prevention based on encouraging results from earlier studies. Living a healthy lifestyle, including regular physical activity, avoiding obesity, and eating primarily a plant-based diet has been associated with a lower risk of colorectal cancer. In addition, noninvasive stool DNA tests for early detection are being studied, which may lessen the reluctance of people to be screened for colorectal polyps and cancer. Behavioral and medical approaches for smoking prevention are ways to reduce the incidence of lung cancer, with antinicotine vaccines on the horizon that may help former smokers to avoid relapse. The US National Lung Screening Trial is testing whether early detection via spiral CT screening will reduce lung cancer mortality. Prevention and earlier detection offer efficient and practical strategies to reduce the cancer burden. Several of the suggestions Mr. Leaf makes, such as developing interdisciplinary collaborations and allocating resources to research earlier in the process of carcinogenesis, have become an integral strategy in the National Cancer Institute's (NCI) approach in the past decade, specifically in the realm of cancer prevention and early detection. For example, an aggressive program to identify biomarkers for earlier detection of cancer--the NCI's Early Detection Research Detection (EDRN)--has identified three promising biomarkers since its establishment in 2000. It collaborates with the National Institute of Standards and Technology and extramural scientists to develop validation standards and to identify the best technologies to use for systematic investigations. If these biomarkers can be validated, they might help to reduce cancer mortality.
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PMID:A favorable view: progress in cancer prevention and screening. 1730 81

Current dogma suggests that the positive correlation between obesity and cancer is driven by white adipose tissue that accompanies obesity, possibly through excess secretion of adipokines. Recent studies in fatless A-Zip/F1 mice, which have undetectable adipokine levels but display accelerated tumor formation, suggest that adipokines are not required for the enhanced tumor development. The A-Zip/F-1 mice are also diabetic and display elevated circulating levels of other factors frequently associated with obesity (insulin, insulin-like growth factor-1, and proinflammatory cytokines) and activation of several signaling pathways associated with carcinogenesis. In view of this information, the risk factors underlying the obesity-cancer link need to be revisited. We postulate that the pathways associated with insulin resistance and inflammation, rather than adipocyte-derived factors, may represent key prevention and therapeutic targets for disrupting the obesity-cancer link.
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PMID:The obesity-cancer link: lessons learned from a fatless mouse. 1736 54

Cells store lipids in droplets. Studies addressing how mammals control lipid-based energy homeostasis have implicated proteins of the PAT domain family, such as perilipin that surrounds the lipid droplets. Perilipin knock-out mice are lean and resistant to obesity. Factors that mediate lipid storage in fungi are still unknown. Here we describe a gene (Mpl1) in the economically important insect fungal pathogen Metarhizium anisopliae that has structural similarities to mammalian perilipins. Consistent with a role in lipid storage, Mpl1 is predominantly expressed when M. anisopliae is engaged in accumulating lipids and ectopically expressed green fluorescent protein-tagged MPL1 (Metarhizium perilipin-like protein) localized to lipid droplets. Mutant M. anisopliae lacking MPL1 have thinner hyphae, fewer lipid droplets, particularly in appressoria (specialized infection structures at the end of germ tubes), and a decrease in total lipids. Mpl1 therefore acts in a perilipin-like manner suggesting an evolutionary conserved function in lipid metabolism. However, reflecting general differences between animal and fungal lineages, these proteins have also been selected to cope with different tasks. Thus, turgor generation by DeltaMpl1 appressoria is dramatically reduced indicating that lipid droplets are required for solute accumulation. This was linked with the reduced ability to breach insect cuticle so that Mpl1 is a pathogenicity determinant. Blast searches of fungal genomes revealed that perilipin homologs are found only in pezizomycotinal ascomycetes and occur as single copy genes. Expression of Mpl1 in yeast cells, a fungus that lacks a perilipin-like gene, blocked their ability to mobilize lipids during starvation conditions.
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PMID:The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism, Appressorial Turgor Pressure, and Virulence. 1752 97

[Avena, N.M., Rada, P., Hoebel B.G., 2007. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience and Biobehavioral Reviews XX(X), XXX-XXX]. The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. "Food addiction" seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. "Bingeing," "withdrawal," "craving" and "cross-sensitization" are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity.
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PMID:Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. 1761 61

That childhood obesity is an alarming public health problem is clear and widely appreciated. What is altogether unclear is what our society should do about it. Some people think the solution lies in using tort law to sue McDonald's, Coca-Cola, and other corporations. We reject that notion. Others believe that government should order specific changes in the behavior of food companies and school officials--and yet, there is little reason for confidence that these "command and control" strategies will make a difference. Instead, we propose "performance-based regulation" of the food industry. This is analogous to the approach our country is now taking with respect to elementary and secondary education (most prominently in the No Child Left Behind legislation). Schools are not told how to achieve better educational results, but better outcomes are demanded of them. This strategy has also been used in the environmental context to reduce harmful power plant emissions, and it has been briefly proposed as a way of regulating cigarette companies. In this Article, we propose that large firms selling food and drink that is high in sugar or fat will be assigned the responsibility of reducing obesity rates in a specific pool of children. A firm's share of the overall responsibility will be based on its share of the "bad' food market, and the children assigned to it will be organized by geographically proximate schools where obesity rates are currently above the plan's nationwide target rate of 8 percent (the actual childhood obesity rate today is approximately 16 percent). Firms that fail to achieve their goals will be subject to serious financial penalties.
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PMID:Fighting childhood obesity through performance-based regulation of the food industry. 1767 77

Dietary salt is a major determinant of fluid intake in adults; however, little is known about this relationship in children. Sugar-sweetened soft drink consumption is related to childhood obesity, but it is unclear whether there is a link between salt and sugar-sweetened soft drink consumption. We analyzed the data of a cross-sectional study, the National Diet and Nutrition Survey for young people in Great Britain. Salt intake and fluid intake were assessed in 1688 participants aged 4 to 18 years, using a 7-day dietary record. There was a significant association between salt intake and total fluid, as well as sugar-sweetened soft drink consumption (P<0.001), after adjusting for potential confounding factors. A difference of 1 g/d in salt intake was associated with a difference of 100 and 27 g/d in total fluid and sugar-sweetened soft drink consumption, respectively. These results, in conjunction with other evidence, particularly that from experimental studies where only salt intake was changed, demonstrate that salt is a major determinant of fluid and sugar-sweetened soft drink consumption during childhood. If salt intake in children in the United Kingdom was reduced by half (mean decrease: 3 g/d), there would be an average reduction of approximately 2.3 sugar-sweetened soft drinks per week per child. A reduction in salt intake could, therefore, play a role in helping to reduce childhood obesity through its effect on sugar-sweetened soft drink consumption. This would have a beneficial effect on preventing cardiovascular disease independent of and additive to the effect of salt reduction on blood pressure.
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PMID:Salt intake is related to soft drink consumption in children and adolescents: a link to obesity? 1849 62

Body composition (BC) assessment provides important information regarding the absolute or relative amount of bone, lean and fat tissue. Different somatometric techniques have been applied in numerous epidemiological and experimental studies, as well as in every day clinical practice. Traditional techniques for BC analysis include skin fold thickness measurements, radioisotope dilution methods, hydrodensitometry and underwater weighing, while newer techniques include bioelectrical impedance analysis (BIA), air displacement plethysmography (ADP), dual energy X-rays absorptiometry (DEXA), computer tomography and magnetic resonance imaging. In addition, positron emission tomography helped to the functional investigation of adipose tissue, in particular of brown tissue. All these techniques have contributed a lot to the understanding of physiological conditions such as exercise training, menopause and ageing, adolescence health parameters, as well as pathological conditions such as disorders of nutrition, cancer, obesity and diabetes mellitus. In obesity, BC contributed to diagnosis and the pathological impact of visceral adipose tissue. In addition, conditions such as pseudo- or hypermuscular obesity and sarcopenia, which are often observed in various endocrine diseases, were investigated in detail by using such methods. During weight loss, some of these methods were quite accurate in measuring changes in fat and lean mass. Apart from anthropometric measurements, a BC measurement if possible should be included in obesity assessment. Measurements of skin fold thickness combined with BIA are quite sufficient for routine clinical practice. However, in specialized clinics and in research, more sophisticated methods like ADP or DEXA are used.
Hell J Nucl Med
PMID:[Body composition analysis in obesity: radionuclide and non radionuclide methods]. 1839 35

This article, by the United Kingdom's last Olympic Marathon Medal winner, Charlie Spedding, and his brother, the pharmacologist, Michael Spedding, covers the difficulties posed by the availability of powerful drugs to ameliorate athletic performance, from an athlete's perspective, particularly in view of the fact that performances are becoming highly optimised with less margin for further physiological improvement. The authors have had long athletic careers and argue that doping not only devalues performance but sport, and exercise, as a whole. Furthermore, the neurotrophic and metabolic changes involved in exercise and training, which can be modified by drugs, are central to health and reflect a part of the epidemic in obesity.
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PMID:Drugs in sport: a scientist-athlete's perspective: from ambition to neurochemistry. 1850 Mar 77


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