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Query: UMLS:C0028754 (obesity)
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Glucocorticoid receptor gene polymorphisms are associated with glucocorticoid hypersensitivity and visceral obesity. Perturbations in HPA axis sensitivity to glucocorticoids implicated in the pathogenesis of major depression may result from functional alterations in the glucocorticoid receptor gene. We 1) examined the prevalence of genotype distribution of specific polymorphisms of the glucocorticoid receptor gene (Bcl1, N363S, rs33388, rs33389) in a subset of women from the P.O.W.E.R. Study (which enrolled 21- to 45-year-old premenopausal women with major depression and healthy controls) and 2) explored whether such polymorphisms were associated with visceral obesity and insulin resistance. Women with major depression had a higher body mass index, a higher waist:hip ratio, and more body fat than did controls. No differences were observed in plasma and urinary cortisol or in insulin sensitivity. The G/G genotype of the Bcl1 polymorphism was significantly more common (p<0.03) in women with major depression (n=52) than in controls (n=29). In addition, GG homozygotes (depressed n=10; controls n=2) had higher waist:hip ratios than did non-GG carriers (p<0.02). N363S, rs33388, and rs33389 polymorphisms were not different between groups. In conclusion, premenopausal women with both major depression and the GG genotype of the Bcl1 polymorphism had greater abdominal obesity compared with non-GG carriers.
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PMID:Glucocorticoid receptor gene polymorphisms in premenopausal women with major depression. 1824 26

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by partially blocking the hydrolysis of dietary triglycerides. A recent meta-analysis evaluated 22 studies lasting for at least 12 months, in obese patients with a mean body mass index of 36.7 kg/m2, where orlistat was associated with hypocaloric diet or behavioral interventions: the net average weight loss was 2.89 kg (confidence interval 2.27-3.51 kg). Considering the principal studies, attrition rate ranged from 33 to 57%. Orlistat significantly decreases waist circumference, blood pressure, total and LDL cholesterol, but has no effect on HDL and triglycerides. This drug significantly reduced the incidence of diabetes only in subjects with impaired glucose tolerance. The major adverse effects with orlistat are mainly gastrointestinal (fatty and oily stool, fecal urgency, oily spotting, fecal incontinence) and attenuate over time. Orlistat should be avoided in patients with chronic malabsorption and cholestasis. Rimonabant is a selective antagonist of cannabinoid type 1 receptor. This drug, by inhibiting the overactivation of the endocannabinoid system, produces anorectic stimuli at the central nervous level, but also has effects on the peripheral systems involved in metabolism control, such as liver, adipose tissue, skeletal muscles, endocrine pancreas, and gastrointestinal apparatus, influencing many processes partially unknown. An ample experimental program named RIO (Rimonabant In Obesity) involved about 6600 obese or overweight patients to identify the effects of rimonabant in weight loss and associated cardiometabolic abnormalities, over and beyond a caloric restriction of 600 kcal in the treatment and placebo arms. In the four double-blind RIO trials published (Rio-North America, RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant 20 mg significantly (p <0.001) reduced weight by 6.3-6.9 kg in the non-diabetic groups vs placebo (-1.5-1.8 kg), whereas in the diabetic subjects enrolled in RIO-Diabetes, weight loss was 5.3 vs 1.4 kg in the placebo group. Attrition rate at 1 year ranged between 40 and 50%, similar to the studies with sibutramine or orlistat. Similarly to weight loss, also waist circumference was significantly reduced by rimonabant. As for cardiometabolic parameters, rimonabant induced a significant increase in HDL cholesterol and a significant decrease in triglycerides. Even if no significant LDL reduction was achieved, the RIO-Lipids study showed a significant decrease in small dense LDL particles, more atherogenic, in rimonabant-treated subjects. Non-diabetic treated patients improved basal insulin and indirect indexes of insulin resistance, while in the RIO-Diabetes study, the only one including diabetics, glycated hemoglobin improved by 0.7% in the active treatment arm vs placebo. The effects on HDL cholesterol and glycated hemoglobin seem in a large percentage unrelated to weight loss. These effects have been confirmed by another trial, named SERENADE, evaluating the treatment in naive diabetic patients. Rimonabant is not recommended in patients with a history of depressive disorders or suicidal ideation and with uncontrolled psychiatric illness, and is contraindicated in patients with ongoing major depression or ongoing antidepressive treatment. In conclusion, despite an enormous advancement in basic research to understand the pathogenetic mechanisms at the base of obesity, the pharmacological research did not reach the therapeutic opportunities available for other chronic conditions, like hypertension and dyslipidemia. However, the few molecules available for clinical practice (sibutramine, orlistat, rimonabant) have shown, when properly used, to contribute to reduce body weight and undoubtedly improve cardiometabolic risk factors. With this preamble, according to current guidelines and pharmacoeconomic studies, patients who might benefit from antiobesity treatment are those with a body mass index > or =30 or 27-29.9 kg/m2 with major obesity-related comorbidities such as hypertension, diabetes, dyslipidemia, obstructive sleep apnea, and metabolic syndrome.
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PMID:[Pharmacological therapy of obesity]. 1877 55

This work, in addition to the peculiar medical aspects of the children obesity, synthesize the experimental findings about the main plasmatic antioxidants (uric acid, ascorbic acid, retinol, coenzyme Q10, lycopene) and the platelet fatty acids profile in groups of children according to the following BMI criteria: 43 with a BMI ranging between 25 and 29; 43 with a BMI ranging between 21.7 e 22.9 and 20 with a BMI ranging between 18.5 e 20; average age 10.49 +/- 2.66. The antioxidants show a particular behaviour: in fact they decrease according to the BMI recorded within the groups. About this issue the international literature is not consistent. Probably different results can be found in more severe condition of obesity. Another important result is for the platelet fatty acid, independently from the BMI, weight etc. compared to the other subjects. The difference found is for the stearic acid, from 15 to 21 point of percentage, compared to all the other groups investigated. In agreement with the international literature, stearic acid seems to have an important role in the control of the platelet activation. This finding, could offer a better possibility to understand the progression of the atherosclerosis towards the ischemic condition, according to the age. The utilisation of particular mathematic models, the Artificial Neural Network, beyond the normal advanced statistic methods, has open to the understanding of phenomena, otherwise, inexplicable. With the Artificial Neural Network (ANN) it has been possible to classify the children using the ANN map built for the depressive condition (platelet fatty acids markers: palmitic acid, linoleic acid, arachidonic acid) and the ANN map built for the ischemic condition (platelet fatty acids markers: oleic acid, linoleic acid, arachidonic acid). Examining the maps, a certain percentage of children seems to be at high risk for several psychiatric conditions with respect to the major depression, while for the ischemic pathology the children are in the same position of the ischemic subjects. Because we know that the children are not ischemic, probably they have the same biochemical characteristics but are protected by the high level of stearic acid and by the high degree of saturation of the platelets. For this reason, children cannot belong to the map area of the major depression, which, in turn, is characterized by a very high degree of unsaturation of the fatty acids. Further studies are needed to better understand the complex situation of the children from the biochemical and psychiatric point of view.
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PMID:[Childhood obesity: recent advances and an experimental contribution]. 1902 56

BMI has been inversely associated with risk of completed suicide in several cohort studies, but putative mechanisms for this association and its generalizability throughout the United States are uncertain. We ascertained recent population-based, state-level data on rates of obesity, completed suicide (by method), firearm ownership, smoking, major depression, income, education, white race, and nonmetropolitan residence, compiled from federal agencies and surveys, and determined the adjusted population-weighted correlations of statewide obesity rates with measures of completed and attempted suicide. Statewide prevalence of obesity was strongly inversely correlated with age adjusted suicide rate (multivariable-adjusted r=-0.66; P<0.001). The correlation was somewhat stronger for rates of nonfirearm-related (r=-0.75; P<0.001) than firearm-related suicides (r=-0.53; P<0.001), and was of similar magnitude as the positive correlations of firearm prevalence with suicide rate (r=0.75; P<0.001) or of obesity with prevalence of diabetes (r=0.41; P=0.006). In analyses of fatal and nonfatal suicidal acts, obesity rates were inversely correlated with rates of suicidal acts using firearms (r=-0.53; P=0.02) and suffocation (r=-0.76; P<0.001) but not other methods. Obesity rates were also inversely correlated with the case-fatality ratios of acts using poisoning (r=-0.51; P=0.01). Thus, statewide rates of obesity are strongly inversely correlated with rates of completed suicide in multivariable analyses, a finding that appears to relate to fewer attempts by suffocation and a lower case-fatality ratio for poisonings, although the mechanism for the inverse correlation with firearm-related suicides requires further elucidation.
Obesity (Silver Spring) 2009 Oct
PMID:BMI and rates of suicide in the United States: an ecological analysis. 1939 May 24

This article provides a detailed review of the association of major depression with coronary heart disease (CHD), examines the biological variables underpinning the linkage and discusses the clinical implications for treatment. When considering the co-morbidity between major depressive disorder (MDD) and CHD it is important to differentiate between (i) the prevalence and impact of MDD in those with existing CHD and (ii) MDD as a risk factor for the development of CHD. Whether the same biological mechanisms are at play in these two instances remains unknown. Depression is common in patients with CHD. Importantly, depression in these patients increases mortality. There is also consistent evidence that MDD is a risk factor for the development of CHD. The relative risk of developing CHD is proportional to the severity of depression and is independent of smoking, obesity, hypercholesterolaemia, diabetes mellitus and hypertension. There is a clear need to identify the underlying neurochemical mechanisms responsible for MDD and their linkage to the heart and vascular system. Of particular interest are activation of stress pathways, including both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, and inflammatory-mediated atherogenesis. Elevated sympathetic activity, reduced heart rate variability and increased plasma cortisol levels have been documented in patients with MDD. In addition to direct effects on the heart and vasculature, activation of stress pathways may also be associated with increased release of inflammatory cytokines such as interleukin-6 and tumour necrosis factor-alpha. Elevated levels of C-reactive protein are commonly observed in patients with MDD. The majority of investigations examining treatment of depression following myocardial infarction have focused on safety and efficacy; there is little evidence to indicate that treating depression in these patients improves survival. Given that strategies for preventive therapy remain incompletely formulated, future research should focus on generating a better understanding of the neurobiology of MDD and heart disease as a basis for rational and effective therapy.
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PMID:Cardiovascular abnormalities in patients with major depressive disorder: autonomic mechanisms and implications for treatment. 1955 86

Research is needed to better elucidate the relationship between obesity and depression, which has been most consistently demonstrated for women, but not for men. We examined exclusively a population-based sample of US women who participated in the 2005 or 2006 National Health and Nutritional Examination Survey. Current depression was defined as having a score of > or =10 (a conventional threshold for moderate symptoms of depression) or meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnostic criteria for major depression on the nine-item Patient Health Questionnaire. Weight and height were measured and BMI was calculated. Waist circumference, a clinical measure of abdominal obesity, was also measured. BMI was positively associated with the probability of moderate/severe depressive symptoms (r = 0.49, P = 0.03) and major depression (r = 0.72, P < 0.0001). The probability curves increased progressively, beginning at BMI of 30. Degree of obesity was an independent risk factor for depression even within the obese population, and women in obesity class 3 (BMI > or =40) were at particular risk (odds ratio (OR) = 4.91, 95% confidence interval (CI): 1.17-20.57), compared to those in obesity class 1 (BMI 30 to <35). Abdominal obesity was positively associated with depressive symptoms, but not major depression, independent of general obesity (BMI). In addition to severe obesity, compromised physical health status, young or middle-aged adulthood, low income, and relatively high education were also independently associated with greater odds of depressive symptoms among obese women. These characteristics may identify specific at-risk subgroups of obese women in which hypothesized causal pathways and effective preventive and therapeutic interventions can be profitably investigated.
Obesity (Silver Spring) 2010 Feb
PMID:Obesity and depression in US women: results from the 2005-2006 National Health and Nutritional Examination Survey. 1959 May

In recent years, there has been an increase in obesity in the general population in both adults and children. Certain mental disorders have been found to co-occur with overweight and obesity. These include binge-eating disorder and bulimia nervosa (nonpurging type), bipolar disorder, certain forms of major depressive disorder, and some severe, chronic mental illness (ie, schizophrenia and schizoaffective disorder). At the same time, some studies have also found that obesity co-occurs with certain mental disorders--specifically binge-eating disorder and mood disorders in females. The co-occurrence of psychiatric disorders (ie, mood and psychotic disorders), binge eating, and overweight or obesity has important public health implications for the treatment of patients with mental disorders, especially since many psychotropic agents can have adverse effects on appetite, binge eating, and weight. Physicians need to keep 2 key points in mind: 1) The treatment of mental disorders in patients with obesity may be different from the treatment of such patients who are not obese, and 2) The treatment of obesity that co-occurs with psychopathology may be different from obesity that is not comorbid with psychopathology.
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PMID:The relationship between severe mental illness and obesity. 1966 51

Sex ratios for selected mental disorders such as major depressive disorder and anxiety disorder are much higher in women than men. Anxiety disorders constitute the most prevalent mental disorder in adults, and affect twice as many women as men. Depression and anxiety exist comorbidly and along with other mental disorders. This article focuses on depression and anxiety in women, and other conditions comorbid with depression or anxiety: cardiac disease, obesity, vitamin D deficiency, and irritable bowel syndrome.
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PMID:Women's mental health: depression and anxiety. 1968 96

Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal development and plasticity and plays a role in learning and memory. Moreover, it is well established that BDNF plays a role in the hypothalamic pathway that controls body weight and energy homeostasis. Recent evidence identifies BDNF as a player not only in central metabolism, but also in regulating energy metabolism in peripheral organs. Low levels of BDNF are found in patients with neurodegenerative diseases, including Alzheimer's disease and major depression. In addition, BDNF levels are low in obesity and independently so in patients with type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic tissues, including skeletal muscle, and exercise increases BDNF levels not only in the brain and in plasma, but in skeletal muscle as well. Brain-derived neurotrophic factor mRNA and protein expression was increased in muscle cells that were electrically stimulated, and BDNF increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta) and enhanced fatty oxidation both in vitro and ex vivo. These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing lipid oxidation in skeletal muscle via activation of AMPK. Thus, BDNF appears to play a role both in neurobiology and in central as well as peripheral metabolism. The finding of low BDNF levels both in neurodegenerative diseases and in type 2 diabetes may explain the clustering of these diseases. Brain-derived neurotrophic factor is likely to mediate some of the beneficial effects of exercise with regard to protection against dementia and type 2 diabetes.
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PMID:Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals. 1974 69

Prior observational studies have investigated the association between obesity and depression but evidence remains weak and mixed. There has been a call for high-quality longitudinal studies to elucidate the etiologic relationship from obesity to depression. The main objective of this study was therefore to investigate whether obesity was a risk factor for depression in a nationally representative sample followed for 12 years. Seven waves of data collection (1994-1995 to 2006-2007) were obtained from the National Population Health Survey (NPHS). Our analyses included 10,545 adults without depression at baseline. Past-year major depression episode (MDE) was assessed from the Composite International Diagnostic Interview-Short Form for Major Depression (CIDI-SFMD). Obesity was estimated using baseline BMI from self-reported weight and height (obesity: BMI > or =30 kg/m(2)). Kaplan-Meier survival curves were generated and Cox proportional hazard regression modeling was used to estimate the risk of MDE by obesity status, controlling for sociodemographic and health and lifestyle variables. We found that obesity at baseline did not significantly predict subsequent MDE in women (adjusted hazard ratio (AHR): 1.03, 95% confidence interval (CI) 0.84-1.26) and negatively predicted MDE in men (HR: 0.71, CI 0.51-0.98), after adjusting for important confounders. In summary, our findings suggest that obesity is a significant (negative) predictor of depression in adult men but not in women. These results moderate prior evidence supporting a positive link from obesity to depression.
Obesity (Silver Spring) 2010 May
PMID:The longitudinal association from obesity to depression: results from the 12-year National Population Health Survey. 1981 9

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