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)

We report a null mutation in the first exon of the human dopamine D4 receptor (DRD4) gene. The mutation is predicted to result in a truncated non-functional protein and is the first natural nonsense mutation found in a human dopamine receptor gene. It occurs with a frequency of about 2% in the general population. The distribution of the mutation was found to be similar in healthy controls and patients suffering from psychiatric diseases which included schizophrenia, bipolar affective disorder and Tourette's syndrome, indicating that heterozygosity for this mutation in the DRD4 gene is not causally related to major psychiatric diseases. We also identified an adult male who is homozygous for this mutation. He shows no symptoms of major psychiatric illness, but he displays somatic ailments including acousticous neurinoma, obesity and some disturbances of the autonomic nervous system. Some of these symptoms might be related to the absence of functional DRD4 protein.
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PMID:Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity. 788 21

A 40 year old woman who was pre-operatively diagnosed as possibly having adrenal myelolipoma is reported. Adrenal myelolipomas are rare, non-functional benign tumours comprising varying amounts of fat and haematopoietic elements. Albeit possibly coincidental, there is a frequent association with obesity, hypertension, and/or diabetes mellitus. A growing number of patients are being diagnosed during ultrasonographic or computerized tomographic scanning for unrelated problems.
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PMID:Adrenal myelolipoma: case report with a review of the literature. 883 93

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder predominantly characterized by obesity, retinal dystrophy, polydactyly, learning difficulties, hypogenitalism and renal malformations, with secondary features that include diabetes mellitus, endocrinological dysfunction and behavioural abnormalities. Despite an initial expectation of genetic homogeneity due to relative clinical uniformity, five BBS loci have been reported, with evidence for additional loci in the human genome; however, no genes for BBS have yet been identified. We performed a genome screen with BBS families from Newfoundland that were excluded from BBS1-5 and identified linkage with D20S189. Fine-mapping reduced the critical interval to 1.9 cM between D20S851 and D20S189, encompassing a chaperonin-like gene. Mutations in this gene were recently reported to be associated with McKusick-Kaufman syndrome (MKKS; ref. 8). Given both the mapping position and clinical similarities of these two syndromes, we screened MKKS and identified mutations in five Newfoundland and two European-American BBS pedigrees. Most are frameshift alleles that are likely to result in a non-functional protein. Our data suggest that a complete loss of function of the MKKS product, and thus an inability to fold a range of target proteins, is responsible for the clinical manifestations of BBS.
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PMID:Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. 1097 51

Melanin concentrating hormone (MCH) is a peptide synthesized in the lateral hypothalamus which stimulates food ingestion and leptin secretion in rodents. In this experiment, we measured the expressions of MCH as well as of its receptor (SLC-1) in the hypothalamus of obese hyperphagic and lean Zucker rats by quantitative real time RT-PCR. MCH mRNA expression in the obese rats was significantly increased by a factor of five (P<0.01) whereas expression of SLC-1 was decreased by more than 50% (P<0.05). Circulating levels of leptin and MCH were increased in the plasma of obese Zucker rats when compared to lean rats (38-fold and 1.7-fold, respectively, P<0.001 and P<0.01). However, individual MCH levels were not directly correlated to leptin levels in the lean (functional leptin receptor) or in the obese (non-functional leptin receptor) Zucker rats. These results indicate that the absence of leptin signaling in rats is associated with an increased hypothalamic expression and circulating release of MCH, contributing to their obesity syndrome.
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PMID:Central and peripheral dysregulation of melanin-concentrating hormone in obese Zucker rats. 1148 40

The neuropeptide melanin-concentrating hormone (MCH) was originally isolated from the pituitary of salmon, in which it causes skin paling. MCH is also found abundantly in mammalian neurons, and has been detected in the lateral hypothalamus and zona incerta, brain regions that are at the center of feeding behavior. Acute central administration of MCH leads to a rapid and significant increase in food intake, while MCH expression changes in states of altered energy balance, such as fasting and obesity. Furthermore, MCH knockout mice tend toward hypophagia and leanness. In 1999, we and four other groups identified an orphan G-protein-coupled receptor (GPCR) as a specific receptor for MCH (MCH-1 receptor). Although a second MCH receptor (MCH-2 receptor) was isolated in humans, it was found to be non-functional or encode a non-functional pseudogene in non-human species, including rodents. The discovery of these MCH receptors permitted the launch of a broad array of drug screening efforts and three MCH-1 receptor antagonists were identified to reduce food intake and body weight. Interestingly, some antagonists unexpectedly produced evidence that blockade of these receptors has antidepressant and anxiolytic activities. The expressions of the MCH receptors, which have been implicated in regulating emotion, stress and motivation, make MCH an excellent candidate for integrating the various homeostatic stimuli necessary for maintaining the proper conditions of energy metabolism and other physiological functions. Finally, the speed at which MCH receptor studies have been undertaken exemplifies the impact that this deorphanized GPCR will have on setting the stage for more detailed physiological studies.
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PMID:Identification of melanin-concentrating hormone receptor and its impact on drug discovery. 1690 61

We investigated the feeding behavior of mice carrying a non-functional 5-hydroxytryptamine-6 receptor (5-HT6). Homozygous mutant mice on C57BL/6 background were grossly normal and showed normal growth when fed a low-fat chow diet. When fed a high-fat diet, the mutant mice consumed approximately 8% less food while gaining approximately 35% less weight over an 11-week study period than did the wild-type controls. Body composition analysis of mice on high-fat feeding showed that the reduced weight gain in the mutant mice was mostly due to reduced fat accumulation. Given the documented role of the serotonin systems in human feeding, our results provide an interesting piece of evidence supporting the development of 5-HT6 receptor antagonists for treating obesity.
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PMID:Reduced sensitivity to diet-induced obesity in mice carrying a mutant 5-HT6 receptor. 1875 68

During the past century, the medical profession has developed a paradigm for the treatment of obesity, which prescribes specific exercise and dietary goals under the umbrella of 'lifestyle change'. It has three components, all of which evolved from origins that had nothing to do with weight control. First, it is individually prescriptive, that is weight loss is considered the responsibility of the individual as contrasted to a societal or group responsibility. Second, it recommends exercise aimed towards structured, or non-functional, activities with a variety of physiological endpoints. Last, dietary goals are defined by calories, exchanges, food groups and various nutritional components. Diets are usually grouped by these goals. This model is unique to America, it is not working and it has also played a causal role in the obesity it is attempting to eliminate. A new model must be developed, which contains an observationally based societal prescription and links activity with functional outcomes and diets, which are food rather than nutritionally based.
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PMID:The emperor's tailors: the failure of the medical weight loss paradigm and its causal role in the obesity of America. 1938 33

According to the adipostat hypothesis for body-weight control, alterations in body weight should always be compensated by adequate alterations in food intake and thermogenesis. Thus, increased thermogenesis should not be able to counteract obesity because food intake would be increased. However evidence is presented here that thermogenesis in different forms (through artificial uncouplers, exercise, cold exposure) may counteract obesity and is not always fully compensated by increased food intake. Correspondingly, a decreased capacity for metaboloregulatory thermogenesis (i.e. non-functional brown adipose tissue) may in itself lead to obesity. This is evident in mice and may be valid for human subjects, as a substantial proportion of adults possess brown adipose tissue, and those with less or without brown adipose tissue would seem to be more prone to obesity. Thus, increased thermogenesis may counteract obesity, without dietary intervention.
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PMID:Thermogenesis challenges the adipostat hypothesis for body-weight control. 1977 94

Metabolic syndrome has been described as the association of insulin resistance, hypertension, hyperlipidemia and obesity. Its prevalence increased dramatically, mainly in developed countries. Animal models are essential to understand the pathophysiology of this syndrome. This review presents the murine models of metabolic syndrome the most often used in pharmacological studies. The most common metabolic syndrome models exhibit a non-functional leptin pathway, or metabolic disorders induced by high fat diets. In a first part, and after a short introduction on leptin, its receptor and mechanism of action, we provide a detailed description of each model: SHROB, SHHF, JCR:LA-cp, Zucker, ZDF, Wistar Ottawa Karlsburg W, and Otsuka Long-Evans Tokushima Fatty rats, ob/ob, db/db, agouti yellow and Mc4R KO mice. The second part of this review is dedicated to metabolic syndrome models obtained by high fat feeding.
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PMID:Murine models for pharmacological studies of the metabolic syndrome. 2317 10

Adrenal pseudocysts are rare lesions that develop within the adrenal glands, generally from vessel ectasia or from degenerative adenomas or hematomas. They are usually non-functional and asymptomatic. The reported potential malignant transformation of an adrenal cyst is ca. 7% and indicates radical excision of these masses. We report the case of a 69-year-old man with hypertension, chronic obstructive pulmonary disease, and obesity in whom microscopic hematuria was detected during a routine examination performed by his family doctor. To investigate the cause of this microscopic hematuria, the patient underwent computed tomography of the abdomen, which showed a well-defined 12-cm lesion of the left adrenal gland with calcification and necrotic components that was compressing the left kidney, pancreas, and spleen. Suspecting adrenal carcinoma, after preoperative staging, a left subcostal laparotomy was performed, with resection of the left adrenal gland, a splenectomy, and resection of the pancreatic tail. The histology showed an adrenal pseudocyst with a fibrous capsule containing amorphous eosinophilic material with calcification and cholesterol crystals. The patient's postoperative course was uneventful, and he was discharged 12 days after surgery.
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PMID:A giant adrenal pseudocyst mimicking an adrenal cancer: case report and review of the literature. 2354 97


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