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

Obesity is a chronic and highly prevalent medical condition associated with increased risk for the development of numerous and sometimes fatal diseases. Despite its severity, there are few anti-obesity agents available on the market. Although psychotropic agents are not approved for the treatment of obesity, they have been used by clinicians as a therapeutic tool in daily clinical practice. The purpose of this article is to review the rationale, as well as the evidence, for the potential use of these agents in obesity treatment. Evidence for the efficacy of psychotropic agents in obesity treatment comes from different sources. The first type of evidence is weight loss observed with treatment in clinical trials of patients with neuropsychiatric syndromes (e.g. mood disorders, epilepsy). A recent example of such findings is the weight reduction reported in clinical trials involving obese patients with binge eating disorder. While randomised, controlled trials specifically designed to investigate the weight loss properties of psychotropic agents in obese patients are the most appropriate source of evidence of anti-obesity action, such trials remain scarce. The most studied psychotropic agents in obesity trials are drugs used in the treatment of mood disorders, i.e. mainly antidepressants and antiepileptics. SSRIs (e.g. fluoxetine, sertraline and fluvoxamine) were amongst the first psychotropic agents investigated in the treatment of obesity. Additional data have also been published for other antidepressants (e.g. venlafaxine, citalopram and bupropion) and antiepileptics (e.g. topiramate and zonisamide). Based on the available data for the efficacy of psychotropic agents in obesity and other related conditions, SSRIs may be considered for the management of certain subgroups of obese individuals with comorbid conditions such as depression, binge eating disorder and type 2 diabetes mellitus. In addition, some newer agents, such as bupropion, topiramate and zonisamide, appear to be promising candidates for selective use in the treatment of obesity. However, further studies are needed to define their possible role as new pharmacological options in the treatment of obesity.
 ...
PMID:Psychotropic drugs in the treatment of obesity: what promise? 1527 May 93

Eating disorders are a group of disease states including anorexia nervosa, bulimia nervosa and binge eating on one end as well as episodic or chronic overeating resulting in obesity at the other end of the spectrum. These disorders are characterized by decreased and/or increased energy intake and are frequently associated with hormonal and metabolic disorders. The discovery of leptin, an adipocyte-secreted hormone acting in the brain to regulate energy homeostasis, and its subsequent study in human physiology have significantly advanced our understanding of normal human physiology and have provided new opportunities for understanding and possibly treating disease states, such as anorexia and bulimia nervosa. It has been recently discovered that leptin levels above a certain threshold are required to activate the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes in men, whereas the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes may be largely independent of circulating leptin levels in humans. In this review, we summarize the latest findings related to the role of leptin in the regulation of several neuroendocrine axes, such as the hypothalamic-pituitary-gonadal and the hypothalamic-pituitary-thyroid axes in humans and discuss its potential pathophysiologic role in eating disorders.
 ...
PMID:The role of leptin in regulating neuroendocrine function in humans. 1533 44

Several lines of evidence indicate an involvement of brain derived neurotrophic factor (BDNF) in body weight regulation and activity: heterozygous Bdnf knockout mice (Bdnf(+/-)) are hyperphagic, obese, and hyperactive; furthermore, central infusion of BDNF leads to severe, dose-dependent appetite suppression and weight loss in rats. We searched for the role of BDNF variants in obesity, eating disorders, and attention-deficit/hyperactivity disorder (ADHD). A mutation screen (SSCP and DHPLC) of the translated region of BDNF in 183 extremely obese children and adolescents and 187 underweight students was performed. Additionally, we genotyped two common polymorphisms (rs6265: p.V66M; c.-46C > T) in 118 patients with anorexia nervosa, 80 patients with bulimia nervosa, 88 patients with ADHD, and 96 normal weight controls. Three rare variants (c.5C > T: p.T2I; c.273G > A; c.*137A > G) and the known polymorphism (p.V66M) were identified. A role of the I2 allele in the etiology of obesity cannot be excluded. We found no association between p.V66M or the additionally genotyped variant c.-46C > T and obesity, ADHD or eating disorders. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.
 ...
PMID:Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder. 1545 98

Binge eating disorder (BED) and night eating syndrome (NES) are putative eating disorders frequently seen in obese individuals. Data suggest that BED fulfills criteria for a mental disorder. Criteria for NES are evolving but at present do not require distress or functional impairment. It remains unclear whether BED and NES, as they are currently defined, are optimally useful for characterizing distinct patient subgroups. We propose that a distinction be made between "eating disorders" and "non-normative" eating patterns without associated distress or impairment. Although non-normative eating patterns may not be considered mental disorders, they may be very important in terms of their impact on body weight and health. More precise behavioral and metabolic characterization of subgroups with eating disorders and non-normative eating behaviors has important implications for understanding the etiology, pathophysiology, and treatment of obesity. Ultimately, better understanding of the many pathways to increased energy intake may lead to targeted strategies for prevention of overweight and obesity in at-risk individuals and populations.
 ...
PMID:Eating disorder or disordered eating? Non-normative eating patterns in obese individuals. 1548 99

Ghrelin is a peripheral gastric peptide involved in the regulation of eating behavior and energy homeostasis. While changes in ghrelin plasma levels have been found in anorexia nervosa, bulimia nervosa (BN) and obesity, no study has assessed circulating ghrelin in binge eating disorder (BED). Therefore, we measured plasma levels of this peptide in women with BED as compared to women with BN, obesity and healthy controls. One hundred and eighty-two drug-free women (56 bulimics, 13 non-obese and 34 obese BED subjects, 28 obese non-binge eating women and 51 non-obese healthy women) underwent psychopathological and nutritional assessments and blood sample collection for glucose and ghrelin assays in the morning. As compared to non-obese healthy women, both non-obese and obese BED women as well as obese non-binge eating women had significantly increased values of body weight, body mass index and body fat mass. Moreover, plasma ghrelin concentrations were significantly decreased in both non-obese (P<0.01) and obese (P<0.0001) BED women as well as in obese non-binge eating women (P<0.001) but not in women with BN. No significant correlations emerged between plasma ghrelin values and the frequency of binge/vomiting in BN subjects or the frequency of bingeing in BED individuals. The reduction of plasma ghrelin in non-obese and obese binge eaters as well as in obese non-binge eaters may represent a secondary change aiming to counteract their positive energy imbalance.
 ...
PMID:Circulating ghrelin is decreased in non-obese and obese women with binge eating disorder as well as in obese non-binge eating women, but not in patients with bulimia nervosa. 1551 98

Eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder) are regarded as psychiatric syndromes that have some relationship to obesity. This review describes current clinical and scientific knowledge concerning the clinical descriptions of these disorders, etiology of each disorder, diagnostic signs, and treatment approaches that have been found to be efficacious. Anorexia nervosa is a very serious eating disorder that is associated with severe medical complications. Anorexia nervosa is very difficult to successfully treat, even when intensive inpatient methods are used. Bulimia nervosa and binge eating disorder are typically less severe eating disorders and are more easily treated using outpatient therapy. Pharmacotherapy has not been found to be an effective treatment for anorexia nervosa, but it has been used successfully with bulimia nervosa and binge eating disorder. Psychotherapy approaches have been successfully employed for all three eating disorders. The review concludes with an integrative perspective that illustrates the similarities and differences of the eating disorders and obesity.
 ...
PMID:Psychological aspects of eating disorders. 1556 39

Melanocortin-4 receptor gene (MC4R) variants are associated with obesity and binge eating disorder (BED), whereas the more prevalent proopiomelanocortin (POMC) and leptin receptor gene (LEPR) mutations are rarely associated with obesity or BED. The complete coding regions of MC4R, POMC, and leptin-binding domain of LEPR were comparatively sequenced in 300 patients (233 women and 67 men; mean +/- SEM age, 42 +/- 1 years; mean +/- SEM body mass index, 43.5 +/- 0.3 kg/m2) undergoing laparoscopic gastric banding. Eating behavior, esophagogastric pathology, metabolic syndrome prevalence, and postoperative weight loss and complications were retrospectively compared between carriers and noncarriers of gene variants with and without BED during 36 +/- 3-month follow-up. Nineteen patients (6.3%) carried 8 MC4R variants, 144 (48.0%) carried 13 POMC variants, and 247 (82.3%) carried 11 LEPR variants. All MC4R variant carriers had BED, compared with 18.1% of noncarriers (P < 0.001). BED rates were similar among POMC and LEPR variant carriers and noncarriers. Gastroscopy revealed more erosive esophagitis in bingers than in nonbingers before and after banding (P < 0.04), regardless of genotype. MC4R variant carriers lost less weight (P=0.003), showed less improvement in metabolic syndrome (P < 0.001), had dilated esophagi (P < 0.001) and more vomiting (P < 0.05), and had fivefold more gastric complications (P < 0.001) than noncarriers. Overall outcome was poorest in MC4R variant carriers, better in noncarriers with BED (P < 0.05), and best in noncarriers without BED (P < 0.001). MC4R variants influence comorbidities and treatment outcomes in severe obesity.
 ...
PMID:Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity. 1558 84

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the 'satiety peptide' cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p < 0.05) with no association with satiety, as in the controls (r = 0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p = 0.07) but no correlation with insulin, as in the controls (r = 0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r = - 0.60) and the CCK response was positively correlated with levels of free testosterone (r = 0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.
 ...
PMID:Impaired cholecystokinin secretion and disturbed appetite regulation in women with polycystic ovary syndrome. 1562 69

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.
 ...
PMID:Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations. 1565 4

Ghrelin is generally influenced by energy balance status and is inversely associated with body mass index (BMI), being reduced in simple obesity, notable exception being Prader Willi syndrome, and elevated in several conditions of undernutrition, including anorexia nervosa (AN). Interestingly, ghrelin levels have also been found elevated in patients with bulimia nervosa (BN) in spite of normal BMI. In humans, intravenous (iv) ghrelin administration induces endocrine (increase in GH, PRL, ACTH and cortisol) and metabolic (increase in glucose and decrease in insulin) effects as well as an increase in appetite and food intake. In AN, ghrelin administration surprisingly leads to a decreased GH response and absence of glycemic variations but normal PRL, ACTH and insulin response. This pattern would reflect a decrease in sensitivity to ghrelin or, alternatively, the metabolic status of AN. To further clarify the function of ghrelin in eating disorders, the endocrine and metabolic response to acute iv ghrelin (1.0 microg/kg) was studied in seven young women with purging BN (BW, BMI, mean+/-SEM: 20.3+/-0.5 kg/m2). Circulating total ghrelin levels were also measured. The results in BW were compared to those recorded in a group of nine healthy women (HW; BMI 22.3+/-2.5 kg/m2). The GH response to ghrelin in BW overlapped with that in HW. Ghrelin administration also led to a similar increase in PRL, ACTH, cortisol and glucose levels in the two groups. Insulin levels were not significantly modified by ghrelin administration in either group. The overlapping endocrine and metabolic response to ghrelin in the two groups occurred with regard to circulating total ghrelin levels which were higher in BW than in HW. In conclusion, BN, a condition of ghrelin hypersecretion, is connoted by a normal endocrine and metabolic response to exogenous ghrelin administration.
 ...
PMID:Hormonal and metabolic responses to acute ghrelin administration in patients with bulimia nervosa. 1580 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>