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

An increase in the risk of cancer is one of the consequences of obesity. The predominant cancers associated with obesity have a hormonal base and include breast, prostate, endometrium, colon and gallbladder cancers. As the basis for understanding the problem of obesity has advanced, a number of new ideas have emerged about the relationship of obesity to cancer. The conversion of androstenedione secreted by the adrenal gland into estrone by aromatase in adipose tissue stroma provides an important source of estrogen for the postmenopausal woman. This estrogen may play an important role in the development of endometrial and breast cancer. Of interest is that experimental animals lacking aromatase or the estrogen receptor alpha are obese. Leptin is one of the many products produced by fat cells and has given rise to the ideas that the fat cell is an endocrine cell and that adipose tissue is an endocrine organ. The increased release of cytokines from this tissue may play a role in the inflammatory state that is associated with obesity. The gut also plays an important role in signaling satiety in response to food intake. Colon cancer is an important human disease, and experimental mice lacking gastrin are obese and have an increased risk of developing colon cancer in response to carcinogenic drugs. Efforts to control obesity through preventive strategies and treatment can be expected to have a benefit in reducing the risk of cancer.
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PMID:The underlying basis for obesity: relationship to cancer. 1242 69

Injection of insulin causes release of HISS (hepatic insulin sensitizing substance) from the liver in the fed state. HISS action accounts for 50-60% of the glucose disposal produced by a wide range of insulin doses (5-100 mU/kg). Although the chemical nature of HISS is unknown, precluding pharmacokinetic studies, the pharmacodynamics of HISS has advanced because of the use of the rapid insulin sensitivity test (RIST) which is a transient euglycemic clamp used following a bolus of insulin. HISS action can be blocked by hepatic denervation and restored by intraportal but not intravenous infusion of acetylcholine or a nitric oxide donor. HISS release is prevented by blockade of hepatic muscarinic receptors, nitric oxide synthase blockers, indomethacin, and animal models of insulin resistance, including chronic liver disease, sucrose feeding, hypertension, aging, obesity, and fetal alcohol exposure. HISS acts on skeletal muscle but not liver, gut, or adipose tissue. HISS is released by insulin in the fed state but decreases to insignificance after 24-hr fasting in rats. Cats and dogs appear to require a longer period of fasting to prevent HISS action. Lack of HISS action is suggested to be the cause of post-meal hyperglycemia and hyperlipidemia in type 2 diabetes and other disease states with similar metabolic dysfunction. The RIST can be carried out up to six times in the same animal, is not affected by pentobarbital anesthesia, and can readily differentiate HISS-dependent and HISS-independent insulin action.
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PMID:Practice and principles of pharmacodynamic determination of HISS-dependent and HISS-independent insulin action: methods to quantitate mechanisms of insulin resistance. 1242 50

The adipose-derived hormone resistin is postulated to link obesity to insulin resistance and diabetes. Here, the infusion of either resistin or the resistin-like molecule-beta (RELMbeta) rapidly induced severe hepatic but not peripheral insulin resistance. In the presence of physiologic hyperinsulinemia, the infusion of purified recombinant resistin, increasing circulating resistin levels by approximately twofold to 15-fold, inhibited glucose metabolism such that lower rates of glucose infusion were required to maintain the plasma glucose concentration at basal levels. The effects of resistin and RELMbeta on in vivo insulin action were completely accounted for by a marked increase in the rate of glucose production. These results support the notion that a novel family of fat- and gut-derived circulating proteins modulates hepatic insulin action.
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PMID:Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. 1456 1

Neurotensin (NT) is a brain-gut tridecapeptide that fulfils a dual function, as a neurotransmitter/neuromodulator in the nervous system, and as a paracrine and circulating hormone in the periphery. Three NT receptors, NTS1, NTS2 and NTS3, have been cloned to date. NTS1 and NTS2 belong to the family of G protein-coupled receptors with seven transmembrane domains, whereas NTS3 is a single transmembrane domain protein that belongs to a recently identified family of sorting receptors. Most of the known peripheral and central effects of NT are mediated through NTS1. NTS2 might take part in the analgesic response elicited by central administration of NT; the biological roles of NTS3 are yet to be discovered. Most NT agonists and non-peptide antagonists developed to date have been studied for their NTS1-targeting abilities. Here, we will discuss the potential diagnostic and therapeutic uses of these compounds in cancer, schizophrenia, obesity and pain suppression.
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PMID:Targeting neurotensin receptors with agonists and antagonists for therapeutic purposes. 1263 Feb 97

Almost 30 years have passed since Gibbs, Young, and Smith demonstrated the ability of exogenously administered cholecystokinin (CCK) to inhibit food intake in rats. This observation was the beginning of very extensive studies into the role CCK plays in the regulation of food intake in mammals. CCK is a brain-gut peptide, which exists in multiple forms. CCK peptides exert their action on two distinct receptor subtypes: CCK-A (Alimentary) now called the CCK1R, mostly expressed peripherally; and CCK-B (Brain), renamed the CCK2R, which is primarily present in the brain. Through the use of subtype-selective agonists and antagonists for the CCK receptor, it was determined that the effect of CCK on feeding was dependent on agonist induced activation of peripheral CCK1 receptors. This discovery was followed by intense research with the goal of identifying small molecule agonists on the CCK1 receptor as potentially useful agents for the treatment of obesity. This review will attempt to summarize the results of this research.
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PMID:CCK1R agonists: a promising target for the pharmacological treatment of obesity. 1267 36

Excess calorie intake in industrialized countries has prompted development of fat substitutes and other lower-calorie dietary items to enhance health. DAG cooking oils, with a 1,3 configuration, taste and have the texture of commonly used TAG cooking oils. Because they are not hydrolyzed to 2-MAG in the gut, the absorption and metabolism of DAG oil differs from that of TAG. Among the physiological differences are lower postprandial lipemia and an increased proportion of FA being oxidized instead of stored. Preliminary studies suggest that these differences in energy partitioning between DAG and TAG may be usefully exploited to reduce the amount of fat stored from cooking oil and oil components of food items. Over 70 million bottles of DAG oil have been sold in Japan since its introduction in February 1999, and the product is being test-marketed in the United States. It is hoped that wider use of DAG oil may provide one additional means of preventing obesity.
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PMID:Nutritional characteristics of DAG oil. 1273 44

The epidemiological data that directly examine whole grain v. refined grain intake in relation to weight gain are sparse. However, recently reported studies offer insight into the potential role that whole grains may play in body-weight regulation due to the effects that the components of whole grains have on hormonal factors, satiety and satiation. In both clinical trials and observational studies the intake of whole-grain foods was inversely associated with plasma biomarkers of obesity, including insulin, C-peptide and leptin concentrations. Whole-grain foods tend to have low glycaemic index values, resulting in lower postprandial glucose responses and insulin demand. High insulin levels may promote obesity by altering adipose tissue physiology and by enhancing appetite. The fibre content of whole grains may also affect the secretion of gut hormones, independent of glycaemic response, that may act as satiety factors. Future studies may examine whether whole grain intake is directly related to body weight, and whether the associations are primarily driven by components of the grain, including dietary fibre, bran or germ.
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PMID:Whole grain consumption and weight gain: a review of the epidemiological evidence, potential mechanisms and opportunities for future research. 1274 53

Epidemiological studies find that whole-grain intake is protective against cancer, cardiovascular disease, diabetes and obesity. Potential mechanisms for this protection are diverse since whole grains are rich in nutrients and phytochemicals. First, whole grains are concentrated sources of dietary fibre, resistant starch and oligosaccharides, carbohydrates that escape digestion in the small intestine and are fermented in the gut, producing short-chain fatty acids (SCFA). SCFA lower colonic pH, serve as an energy source for the colonocytes and may alter blood lipids. These improvements in the gut environment may provide immune protection beyond the gut. Second, whole grains are rich in antioxidants, including trace minerals and phenolic compounds, and these compounds have been linked to disease prevention. Additionally, whole grains mediate insulin and glucose responses. Although lower glycaemic load and glycaemic index have been linked to diabetes and obesity, risk of cancers such as colon and breast cancer have also been linked to high intake of readily-available carbohydrate. Finally, whole grains contain many other compounds that may protect against chronic disease. These compounds include phytate, phyto-oestrogens such as lignan, plant stanols and sterols, and vitamins and minerals. As a consequence of the traditional models of conducting nutrition studies on isolated nutrients, few studies exist on the biological effects of increased whole-grain intake. The few whole-grain feeding studies that are available show improvements in biomarkers with whole-grain consumption, such as weight loss, blood lipid improvement and antioxidant protection.
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PMID:Why whole grains are protective: biological mechanisms. 1274 67

CART peptides are relatively novel neuropeptides involved in feeding, drug reward and stress. They are formed from a proCART polypeptide that is 89 amino acids in length in the human version. Fragments 42-89 and 49-89 are behaviorally active in feeding and locomotion as well and other functions. These peptides are highly abundant and widely but discretely distributed in the brain, gut, pituitary, adrenals and pancreas. The presence of CART immunoreactivity in specific nuclei of the hypothalamus has led to an examination of icv-injected CART peptides effects on feeding, which have proven to be significantly anorectic. Studies of transgenic animals and humans have also demonstrated a linkage to both obesity and anorexia. Similarly, the localization of CART to sub-regions of the mesolimbic dopamine system has led to demonstration of the effects of CART peptides on locomotor activity and conditioned place preference when injected into the ventral tegmental area (VTA), which are psychostimulant-like in quality. These findings also suggest that CART has the capacity to modulate mesolimbic dopamine, which could have implications for the treatment not only of psychostimulant abuse but also for the treatment of other disorders with mesolimbic dopamine involvement, such as schizophrenia. Other lines of evidence also show that CART peptides are involved in fear and startle behaviors which may have implications for understanding anxiety and stress. An important part of the development of CART mimetics and related drugs would be the identification of CART receptors. At the present time such receptors have not been identified, and much effort should be directed at this problem. Nonetheless, CART peptides offer interesting targets for new drug development for obesity and, potentially, a number of other disorders.
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PMID:CART peptides as targets for CNS drug development. 1276

Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers. The gut hormones ghrelin and peptide YY are secreted from the gut in response to changes to nutritional status. While food intake is stimulated by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology of ghrelin and peptide YY are discussed, focusing on the adaptive changes in diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important therapeutic targets in the quest to find an effective antiobesity treatment.
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PMID:Gut and mind. 1280 49


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