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

Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.
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PMID:Etiology and pathogenesis of uterine leiomyomas: a review. 1282 76

Stroke morbidity increases with age. That is the reason why it affects especially the middle aged and elderly. Life expectancy is longer for females than males by 10 years, that is why stroke is a major problem in women. Women die twice more frequently from stroke than men (16% vs. 8%). Stroke risk factors are basically the same in spite of gender. The most important are hypertension, diabetes, dyslipidaemia, atrial fibrillation, coronary heart disease, previous stroke, smoking, alcohol abuse, obesity and lack of physical activity. Their impact, however, is different in males and females. Women with diabetes, atrial fibrillation, myocardial infarction, obese, drinking excessive amounts of alcohol and smoking are more likely to suffer of stroke than males with the same burden. A less favourable outcome after stroke has been observed in female patients--higher mortality rates and disability. It is possible that poor prognosis is related to a drop in blood estrogen concentration after menopause. Estrogen replacement therapy has not proved to be beneficial in preventing stroke and improving outcome. There are several specific conditions: pregnancy, migraine in women associated with the occurrence of stroke.
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PMID:[Does gender exert influence on stroke?]. 1456 Jul

There is growing concern over the effects of sedentary lifestyles on the health of young people. Recent rapid increases in juvenile obesity have received a great deal of attention in the scientific and popular press and have been attributed partly to television viewing, computer games and other sedentary behaviours. These are thought to compete with physical activity. There is a 'moral panic' concerning the 'couch kids' culture in modern western society. Project STIL (Sedentary Teenagers and Inactive Lifestyles) at Loughborough University is investigating 'what young people do' and focuses on active and inactive pursuits chosen in their leisure time. The following issues are addressed in this paper with specific reference to young people: how do we define 'sedentary behaviour' and do key sedentary behaviours displace physical activity? Are key sedentary behaviours obesogenic? What are the secular trends for children and youth for TV viewing? Our results for young people suggest that: 1. TV viewing and video-game playing are largely uncorrelated with physical activity, suggesting that there is time for both 2. meta-analytic findings show that body fatness is not related in any clinically meaningful way with key sedentary behaviours 3. although more children and youth have greater access to TVs than in previous generations, the amount of TV watched per head has not changed for 40 years. Preliminary findings from Project STIL suggest that inactivity is more complex that we sometimes think. Indeed, measures of 'couch potato-ism', such as TV viewing, may be inappropriate markers of inactivity.
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PMID:Physical activity and sedentary behaviours in youth: issues and controversies. 1497 Nov 90

Estrogens, acting through its two receptors, ESR1 (hereafter designated ER alpha) and ESR2 (hereafter designated ER beta), have diverse physiological effects in the reproductive system, bone, cardiovascular system, hematopoiesis, and central and peripheral nervous systems. Mice with inactivated ER alpha, ER beta, or both show a number of interesting phenotypes, including incompletely differentiated epithelium in tissues under steroidal control (prostate, ovary, mammary, and salivary glands) and defective ovulation reminiscent of polycystic ovarian syndrome in humans (in ER beta-/- mice), and obesity, insulin resistance, and complete infertility (both in male and female ER alpha-/- mice). Estrogen agonists and antagonists are frequently prescribed drugs with indications that include postmenopausal syndrome (agonists) and breast cancer (antagonists). Because the two estrogen receptors (ERs) have different physiological functions and have ligand binding pockets that differ enough to be selective in their ligand binding, opportunities now exist for development of novel ER subtype-specific selective-ER modulators.
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PMID:Estrogen receptor beta in health and disease. 1603 96

This review presents a comprehensive, evenhanded evaluation of the evidence from experimental, in vitro and human studies associating environmental and therapeutic factors with risk of colorectal cancer. Life styles correlated with the greatest increase in colorectal cancer risk are the ones that typify a diet rich in fat and calories, alcohol drinking and tobacco smoking, and low intake of vegetable, fruits and fibers, referred to as a "western diet," as well as sedentary style (i.e., no- or low-exercise). This kind of life style has also been associated with other chronic diseases (other cancers, obesity, dyslipedemia, diabetes, hypertension cardiovascular, and hypertension). The evidence does not implicated red meat as a risk factor, and fiber has been shown to protect against colorectal adenomas and carcinomas. Calcium, vitamin D, folate, and some antioxidant vitamins and minerals (gamma-tocopherol and selenium) have protective effects, and daily exercise for > or =30 min results in a significant decrease in risk. Estrogen use (hormone replacement therapy) substantially reduces colorectal cancer risk in postmenopausal women. Nonsteroidal anti-inflammatory drugs (e.g., aspirin) in excessive doses is protective, especially in high risk populations, but the side effects of its use and cost incurred due to its continued intake over long periods must be carefully scrutinized before any recommendations are made for the general public.
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PMID:Effect of diet, life style, and other environmental/chemopreventive factors on colorectal cancer development, and assessment of the risks. 1629 19

Peroxisome Proliferator Activated Receptors (PPARs) are regulators of metabolic pathways mainly of lipid metabolism and energy balance. Their medical importance is given by the fact that they have been implicated in development of insulin resistance, obesity and atherosclerosis. In recent years, major progress has been made in understanding the molecular basis of the function of these receptors. As a result of structural studies and identification of putative natural as well as synthetic ligands and activators of PPARs a new concept emerged and new drugs are on their ways to the clinic. The concept of Selective PPAR Modulators (SPPARM) was suggested by analogy to Selective Estrogen Receptor Modulators (SERM). SPPARMs activate the receptors in distinct ways leading to differential gene expression and biological response. The key features in understanding their action is most likely at the molecular details of ligand binding and the subsequently induced conformational changes as well as cofactor binding. A key aspect of this is that unlike classical steroid hormone receptors such as the retinoic acid receptor, the PPAR receptors have a rather large ligand-binding pocket which is not filled with the ligand entirely and the ligand also stabilizes the receptor's structure. The liganded receptor can have distinct conformations and this leads to different binding affinities for the various cofactors (coactivators and corepressors). In this review, we will introduce this concept, review the literature that supports it and present an overview of the receptor selective ligands including data about their mechanism of action and biological effects.
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PMID:Selective modulators of PPAR activity as new therapeutic tools in metabolic diseases. 1661 Nov 63

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

Estrogens are essential for fertility and also have important effects on regulation of adiposity and the euglycemic state. We report here that lipin1, a candidate gene for lipodystrophy and obesity that is a phosphatidic acid phosphatase critical in regulation of cellular levels of diacylglycerol and triacylglycerol and a key regulator of lipid utilization, is rapidly and robustly down-regulated in the uterus by estradiol via the estrogen receptor. Lipin1 is expressed predominantly in the uterine luminal and glandular epithelium, and during the estrous cycle, lipin1 is lowest when blood levels of estrogen are highest. Lipin1 is expressed throughout all cells in the liver of ovariectomized female mice, and a sustained down-regulation is observed at the mRNA, protein and immunohistochemical levels after estrogen administration. Because the coupling of proper energy use and availability is central to reproduction, we also investigated expression of lipin1 in the uterus and liver of several mouse models of diabetes. Nonobese diabetic (NOD) mice, which have high blood levels of estrogen and impaired fertility, were severely deficient in lipin1 in the uterus and liver, which, interestingly, could be restored by insulin treatment. By contrast, nonobese diabetic/severe combined immunodeficient (NOD-SCID) mice, which do not develop diabetes, showed normal levels of lipin1. Our findings of lipin1 regulation by estrogen in two key target organs suggest a new role for this lipid-regulating phosphatase not only in central metabolic regulation but also in uterine function and reproductive biology. Estrogen regulation of lipin1 may provide a mechanistic link between estrogens, lipid metabolism, and lipid signaling.
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PMID:Lipin1 regulation by estrogen in uterus and liver: implications for diabetes and fertility. 1746 59

Women have a higher percentage of body fat than men, and there is a gender-specific difference in fat distribution: Females tend to accumulate fat around the hips, buttocks, and thighs while men have a larger intra-abdominal (visceral) fat mass. After menopause, there is a redistribution of fat depots, and post-menopausal women develop increased amounts of visceral fat. The risk of developing obesity-related diseases is significantly lower in pre-menopausal women compared to men, a difference that is abolished after menopause, suggesting that the female sex steroid estrogen influences adipogenesis and adipose metabolism. Experimentally, estrogen increases the size and number of subcutaneous adipocytes and attenuates lipolysis. Post-menopausal women also develop a more atherogenic lipid pattern and decreased levels of the prothrombotic protein plasminogen activator inhibitor-1, which attenuates fibrinolysis. Pathologically increased circulating cortisol concentration is associated with dysmetabolic features e.g., central obesity, elevated blood pressure, insulin resistance, and dyslipidemia. In "simple obesity," glucocorticoid production is elevated. Peak levels of circulating cortisol are however low or normal, possibly because of increased clearance and/or tissue-specific changes in cortisol production. In addition to the adrenal production of cortisol, cortisol is also generated in adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inactive cortisone to active cortisol. The enzyme activity in subcutaneous fat increases with increasing body weight. Estrogen seems to have a tissue-specific influence on 11betaHSD1 enzyme activity, attenuating it in liver, kidney, and testis but upregulating 11betaHSD1 mRNA expression in preadipocytes from women. In the present review, we summarize and discuss the interaction between glucocorticoids and sex steroids and their influence on adipocyte metabolism.
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PMID:Estrogens and glucocorticoid hormones in adipose tissue metabolism. 1804 37

Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.
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PMID:Impairment of the natriuretic peptide system in follitropin receptor knockout mice and reversal by estradiol: implications for obesity-associated hypertension in menopause. 1806 89


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