Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many complex biological programs are controlled at the level of gene transcription by DNA binding transcription factors. Recent studies have revealed a novel mode of regulation by coactivator proteins, best illustrated by the PGC-1 family of coactivators. These factors are highly responsive to a variety of environmental cues, from temperature to nutritional status to physical activity, and they coordinately regulate metabolic pathways and biological processes in a tissue-specific manner. Notably, the PGC-1 coactivators play a critical role in the maintenance of glucose, lipid, and energy homeostasis and are likely involved in the pathogenic conditions such as obesity, diabetes, neurodegeneration, and cardiomyopathy. These actions also raise new opportunities for the development of novel therapeutics.
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PMID:Metabolic control through the PGC-1 family of transcription coactivators. 1605 85

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of a metabolic syndrome of diabesity comprised of age-related degenerative diseases and obesity in a outbred stock of Sprague-Dawley (SD) rats [Crl:CD (SD) IGS BR]. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights, carcass analysis, in-life data including estrous cyclicity, and histopathology were determined. At 6-7 weeks of age SD rats had 6% body fat. AL-feeding resulted in hypertriglyceridemia, hypercholesterolemia, and dietary-induced obesity (DIO) by study week 14, with 25% body fat that progressed to 36-42% body fat by 106 weeks. As early as 14 weeks, key biomarkers developed for spontaneous nephropathy, cardiomyopathy, and degenerative changes in multiple organ systems. Early endocrine disruption was indicated by changes in metabolic and endocrine profiles and the early development and progression of lesions in the pituitary, pancreatic islets, adrenals, thyroids, parathyroids, liver, kidneys, and other tissues. Reproductive senescence was seen by 9 months with declines in estrous cyclicity and pathological changes in the reproductive organs of both sexes fed AL or moderate DR, but not marked DR. The diabesity syndrome in AL-fed, DIO SD rats was readily modulated or prevented by moderate to marked DR. Moderate DR of balanced diets resulted in a better toxicology model by significantly improving survival, controlling adult body weight and obesity, reducing the onset, severity, and morbidity of age-related renal, endocrine, metabolic, and cardiac diseases. Moderate DR feeding reduces study-to-study variability, increases treatment exposure time, and increases the ability to distinguish true treatment effects from spontaneous aging. The structural and metabolic differences between the phenotypes of DIO and DR SD rats indicated changes of polygenic expression over time in this outbred stock. AL-overfeeding of SD rats produces a needed model of DIO and diabesity that needs further study of its patterns of polygenic expression and phenotype.
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PMID:Diabesity: a polygenic model of dietary-induced obesity from ad libitum overfeeding of Sprague-Dawley rats and its modulation by moderate and marked dietary restriction. 1620 39

Fifty type 2 diabetes patients (25 of them being hypertensive) who had no cardiac symptoms had their left ventricular function assessed. There were 24 female and 26 male diabetes patients evaluated, along with a control group of 50 healthy subjects. The patients and controls underwent full clinical evaluation, which included physical examination, blood biochemistry (urea and electrolyte; creatinine, creatinine clearance; fasting blood and two-hour postprandial glucose levels, lipid profile), electrocardiograph, chest radiograph, and echocardiograph. The hypertensive diabetes patients had higher cholesterol levels, and 50% had levels >5.0 mmol/L. Sixteen patients had cataracts, 14 had background retinopathy, 12 had peripheral neuropathy, and 7 had peripheral vascular disease. The subjects had significantly lower ejection fraction than controls, and fractional shortening showed a similar pattern. Eight patients had ejection fraction <50% compared to none of the controls. Sixty-six percent of the subjects and 30% of the controls had diastolic dysfunction (reverse E/A ratio, prolonged deceleration time, and lower deceleration rate), respectively, but the diabetes patients did not show any difference. Diastolic dysfunction correlated significantly with age, fasting blood glucose, and two-hour postprandial glucose. The subjects had higher left ventricular mass (LVM) than controls. The LVM correlated significantly positively with diastolic blood pressure, systolic blood pressure, and pulse pressure. Subclinical diabetic cardiomyopathy exists in our patients; in addition, other risk factors for cardiomyopathy and coronary artery disease exist, including hypertension, hypercholesterolemia, and obesity.
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PMID:Left ventricular function in type 2 diabetes patients without cardiac symptoms in Zaria, Nigeria. 1626 87

Cardiomyopathy is associated with both rare genetic metabolic abnormalities and highly prevalent diseases characterized by elevated serum triglycerides and nonesterified fatty acids, such as obesity and type 2 diabetes. In these disorders, an imbalance between fatty acid uptake and utilization leads to the inappropriate accumulation of free fatty acids and neutral lipids within cardiomyocytes. Through the process of lipotoxicity, this lipid overload causes cellular dysfunction, cell death, and eventual organ dysfunction. This review focuses on lipotoxicity in the heart, with an emphasis on the contribution of this process to the pathogenesis of cardiomyopathy associated with obesity, diabetes, and the metabolic syndrome. The magnitude of the current worldwide epidemic of obesity and type 2 diabetes suggests that understanding the pathogenesis of cardiac complications associated with these diseases will contribute substantially to improvements in health care.
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PMID:Lipotoxicity in the heart. 1638 96

Obesity has been identified as an independent risk factor for coronary heart disease and congestive heart failure. Although congestive heart failure can be secondary to coronary heart disease, in morbid obesity these conditions can be independent. Cardiac structure and function can be altered even in the absence of systemic hypertension and underlying organic heart disease. In obese patients total blood volume increases and creates a high cardiac output state that may cause ventricular dilatation and ultimately eccentric hypertrophy of the left (and possibly the right) ventricle. Eccentric left ventricular hypertrophy produces diastolic dysfunction. Systolic dysfunction may ensue due to excessive wall stress if wall thickening fails to keep pace with dilatation. This disorder is referred to as obesity cardiomyopathy. The frequent coexistence of systemic hypertension in obese individuals facilitates development of left ventricular dilatation and hypertrophy. Congestive heart failure may occur and may be attributable to left ventricular diastolic dysfunction or to combined diastolic and systolic dysfunction. The risk of coronary heart disease seems to be more strictly correlated to central obesity than to increased body mass index. Insulin resistance seems to be the key factor that links obesity and ischaemic heart disease. In such a condition the so called Syndrome X appears. It is characterized by: obesity, systemic hypertension, diabetes mellitus, hypertriglyceridaemia and reduced HDL cholesterol levels. Considering that left ventricular hypertrophy is often present, many risk factors coexist in obese patients. Weight loss is very useful in obese patients. It may reduce mortality and morbidity for coronary heart disease and delay or avoid the appearance of congestive heart failure. It is proved that after weight loss, blood pressure, glucose, cholesterol, triglycerides and left ventricular mass decrease.
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PMID:[Obesity and the heart]. 1649 82

Obesity is a major risk factor for heart disease. In the face of obesity's growing prevalence, it is important for physicians to be aware of emerging research of novel mechanisms through which adiposity adversely affects the heart. Conventional wisdom suggests that either hemodynamic (that is, increased cardiac output and hypertension) or metabolic (that is, dyslipidemic) derangements associated with obesity may predispose individuals to coronary artery disease and heart failure. The purpose of this review is to highlight a novel mechanism for heart disease in obesity whereby excessive lipid accumulation within the myocardium is directly cardiotoxic and causes left ventricular remodeling and dilated cardiomyopathy. Studies in animal models of obesity reveal that intracellular accumulation of triglyceride renders organs dysfunctional, which leads to several well-recognized clinical syndromes related to obesity (including type 2 diabetes). In these rodent models, excessive lipid accumulation in the myocardium causes left ventricular hypertrophy and nonischemic, dilated cardiomyopathy. Novel magnetic resonance spectroscopy techniques are now available to quantify intracellular lipid content in the myocardium and various other human tissues, which has made it possible to translate these studies into a clinical setting. By using this technology, we have recently begun to study the role of myocardial steatosis in the development of obesity-specific cardiomyopathy in humans. Recent studies in healthy individuals and patients with heart failure reveal that myocardial lipid content increases with the degree of adiposity and may contribute to the adverse structural and functional cardiac adaptations seen in obese persons. These studies parallel the observations in obese animals and provide evidence that myocardial lipid content may be a biomarker and putative therapeutic target for cardiac disease in obese patients.
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PMID:Adiposity of the heart, revisited. 1701 81

Cardiovascular disease is the leading cause of morbidity and mortality in both genders. Although premenopausal women display a lower prevalence in cardiovascular diseases compared with age-matched men, they lose this ''female advantage'' following menopause. There are significant gender differences in a wide spectrum of cardiovascular incidence, ranging from delayed disease onset to higher prevalence of comorbid diseases for females. Several factors have been suggested to contribute to such difference in cardiovascular incidence including sex hormones, gender-specific intrinsic organ function, difference in body size and cardiovascular risk factor profiles (e.g., use of tobacco and alcohol, hypertension, diabetes mellitus, dyslipidemia, obesity, sedentary lifestyle and atherogenic diet). A gender difference also exists for diabetes and diabetic complications. Heart diseases exhibits a 2-fold and a 5-fold increase in men and women with diabetes, respectively. Although female hearts are usually more tolerable to stress insults than their male counterparts, female sex hormone such as estrogen interacts with diabetic risk factors to precipitate cardiomyopathy. This review aims at recaping our knowledge on gender difference in diabetic heart disease with an emphasis on disease pathogenesis. Deficits and obstacles to optimal risk factor management in diabetic women are also discussed in an effort to improve the overall cardiovascular health of diabetic women.
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PMID:Cardiac health and diabetes mellitus in women: problems and prospects. 1673 4

Cardiovascular diseases (CVDs) may have their origin before birth: the combination of being small at birth and having an overly rich post-natal diet increases the likelihood of obesity and of acquiring a specific metabolic syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD and mortality is very low in women of reproductive age but rises to a significant level in older women. In this article, we discuss CVD in relation to hormonal contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women and menopause in older women. Women with PCOS have a higher risk of diabetes and hypertension, but studies to date have not shown an effect on CVD events. Use of combined hormonal contraception has only small effects on CVD because of the low baseline incidence of myocardial infarction (MI), stroke and venous thromboembolism (VTE) among young women. Women with existing risk factors or existing CVD, however, should consider alternative contraception. In pregnancy, CVD is rare, although, in the West, it now accounts for a significant proportion of maternal mortality as the frequency of obstetrical causes of mortality has substantially declined. The frequency of VTE is 15 per 10,000 during pregnancy and the post-partum period. In older women, menopause causes a slightly higher risk of MI after allowing for age, although there is substantial heterogeneity in the results of studies on menopause and age at menopause and MI. A larger effect might have been expected, because estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic disease, estrogen increases the risk of myocardial disease through the effects on plaque stability and clot formation. Recent trial results indicate that hormone treatment in menopause does not favourably affect the risk of MI, stroke or other vascular disease. Thus, prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment of hypertension, hyperglycaemia and hyperlipidaemia.
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PMID:Hormones and cardiovascular health in women. 1680 76

Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m(2.7)) than did control subjects (37 +/- 8 g/m(2.7), P < .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P < .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1 +/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.
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PMID:Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study. 1688 Jan 4

Mitochondria play a pivotal role in the life of cells, controlling diverse processes ranging from energy production to the regulation of cell death. In humans, numerous pathological conditions have been linked to mitochondrial dysfunction. Cancer, diabetes, obesity, neurodegeneration, cardiomyopathy and even aging are all associated with mitochondrial dysfunction. Over 400 mutations in mitochondrial DNA result directly in pathology and many more disorders associated with mitochondrial dysfunction arise from mutations in nuclear DNA. It is counter-intuitive then, that a class of mitochondrially defective mutants in the nematode Caenorhabditis elegans, the so called Mit (Mitochondrial) mutants, in fact live longer than wild-type animals. In this review, we will reconcile this paradox and provide support for the idea that the Mit mutants are in fact an excellent model for studying human mitochondrial associated diseases (HMADs). In the context of the 'Mitochondrial Threshold Effect Theory', we propose that the kinds of processes induced to counteract mitochondrial mutations in the Mit mutants (and which mediate their life extension), are very likely the same ones activated in many HMADs to delay disease appearance. The identification of such compensatory pathways opens a window of possibility for future preventative therapies for many HMADs. They may also provide a way of potentially extending human life span.
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PMID:Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. 1694 97


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