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.
Hum Mol Genet 1994 Dec
PMID:Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity. 788 21

Adipocytes from genetically obese (ob/ob) mice display an impaired response to beta-adrenergic stimulation, but the molecular defects have not been unequivocally identified. The expression and functional activity of the beta 1-, beta 2-, and beta 3-adrenergic receptor (AR) subtypes in white and brown adipose tissue from genetically lean and obese (ob/ob) mice were compared. Three beta 3AR transcripts of 2.1, 2.6, and 3.5 kilobases were identified in adipose tissue from lean mice by Northern blotting. All three beta 3AR mRNA species were dramatically reduced (by approximately 300-fold) in 12-week-old obese mice compared to those in lean animals. beta 1AR mRNA levels were also reduced (by approximately 4-fold) in obese mice, whereas beta 2AR mRNA levels were not significantly changed. The functional consequences of these changes in beta 3AR and beta 1AR expression were assessed by measuring beta-agonist-stimulated adenylyl cyclase activity in adipocyte plasma membranes with subtype-selective beta-adrenergic agonists and antagonists. Dose-response curves with epinephrine from lean mice were best fit to a two-component model comprised of 23% high affinity (K(act) = 1.42 x 10(-7) M) and 77% low affinity (K(act) = 1.67 x 10(-5) M) components, corresponding to activation of beta 1AR and beta 2AR conjointly, and beta 3AR, respectively. The beta 1AR-selective antagonist CGP20712A reduced the high affinity component to about 10%, whereas the nonselective beta-antagonist propranolol eliminated the high affinity component. The beta 3AR-selective agonist BRL37344 stimulated adenylyl cyclase activity in lean membranes to a slightly lesser extent than epinephrine, but was more potent (73% high affinity component; K(act) = 3.61 x 10(-8) M). In obese mice, stimulation of adenylyl cyclase by all agonists was severely blunted and was best fit to a single class of sites. Studies with CGP20712A or the beta 2AR-selective antagonist ICI118,551 indicated that this residual response was predominantly beta 2AR in character. Expression of beta AR subtypes in both brown and white adipose tissue of weanling obese mice (4-5-weeks of age) was also affected, but to a lesser extent, consistent with the progressive severity of obesity with age. Together the reduction in expression of the beta 3AR and beta 1AR impairs the beta-agonist-stimulated adenylyl cyclase response over a broad concentration range by greatly lowering the maximum stimulation and shifting the adrenergic sensitivity at low concentrations from a mixed beta 1AR/beta 2AR response to predominantly beta 2AR.
Mol Endocrinol 1994 Apr
PMID:Impaired expression and functional activity of the beta 3- and beta 1-adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice. 791 50

The objective was to determine the effects of persistent obesity on amino acid enzymes in white (WAT) and brown (BAT) adipose tissues. Dietary obesity was induced by feeding a cafeteria diet ad libitum for 3 months, then it was removed and the obese animals received the same diet as controls for 5 months. Dietary-induced obesity was persistent as obese rats showed a stable, higher body weight than controls (26%). Key enzymes of alpha-amino nitrogen metabolism were studied and results showed reduced activities in obese rats: glutamine synthetase (45%), AMP deaminase (52%), alanine aminotransferase (66%) and glutamate dehydrogenase (68%) in BAT, whereas WAT of obese animals only showed lower aspartate aminotransferase activity (47%) with respect to the controls. We can conclude that these adaptations in amino acid metabolism were exclusively dependent on the obese status as they were observed in an obesity model in which obese rats eat the same diet as controls.
Biochem Mol Biol Int 1994 Apr
PMID:Brown and white adipose tissue adaptive enzymatic changes on amino acid metabolism in persistent dietary-obese rats. 791 90

Amino acid concentration in blood cells and plasma and the calculated blood cell to plasma gradients (C/P) were measured in different blood vessels (aortic artery and portal, hepatic, iliac and renal veins) from both control and cafeteria diet obese rats. Essential amino acids are increased in plasma in all blood vessels in obese rats. The iliac vein was the only vessel in which cell concentration of amino acids, and mainly the mean of the combined non-essential amino acids, was affected by obesity. Only in the iliac vein were C/P values of the combined amino acids, including both essential and non-essential, significantly lower in obese versus control rats. These results also show that there are differences between sampling sites which should be noted in the design of physiological studies of amino acid metabolism.
Biochem Mol Biol Int 1994 Jun
PMID:Blood amino acid compartmentation in obese rats is specifically altered in the iliac vein. 795 Oct 60

The effects of long-term treatment of C57BL/6J (ob/ob) mice with a synthetic carboxylterminal sequence of human growth hormone, hGH 177-191, were investigated. Results indicate that the hGH 177-191 reduced the cumulative body weight gain, and decreased the adipose tissue mass. The lipogenesis in adipose tissues was significantly inhibited by the treatment with hGH 177-191. These findings support the suggestion that hGH 177-191 is the functional domain of hGH for the antilipogenic actions of the intact hormone both in vivo and in vitro. The hGH 177-191 peptide has the potential to be an effective compound for the treatment of human obesity and for the improvement of meat qualities in farm animals.
Biochem Mol Biol Int 1994 Aug
PMID:Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. 798 48

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Individuals with this disorder also have an increased incidence of hypertension, diabetes mellitus, and renal and cardiac anomalies. We previously identified a locus on chromosome 16 causing this disorder, and provided evidence that Bardet-Biedl syndrome is heterogeneous. In this study, we identify another Bardet-Biedl syndrome locus on chromosome 3 and confirm the non-allelic heterogeneity of this disorder in Bedouin populations. In addition, we demonstrate the feasibility of using pooled DNA samples from members of large kindreds as an efficient approach to homozygosity mapping.
Hum Mol Genet 1994 Aug
PMID:Identification of a Bardet-Biedl syndrome locus on chromosome 3 and evaluation of an efficient approach to homozygosity mapping. 798 10

The weight gain and hyperphagia induced by chronic administration of sulpiride in female rats were not prevented by the concomitant administration of an extra source of sodium. In addition, serum sodium levels were not affected, but potassium levels were significantly reduced by sulpiride administered for 1 week. These results suggest that sulpiride-induced obesity in rats is not related to sodium imbalance. The mechanism for the decrease in serum potassium levels and its relation with sulpiride-induced weight gain warrant further investigation.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Hyponatremia and neuroleptic-induced obesity in rats. 799 68

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. Our results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.
Somat Cell Mol Genet 1993 Nov
PMID:Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23. 812 15

Considerable variability exists among individuals in the response of plasma cholesterol to changes in dietary fat and cholesterol, and obesity is one variable reported to affect this response. This study was performed to determine the relationship between body fat and changes in plasma cholesterol in cynomolgus monkeys fed a high-fat cholesterol-containing diet for 12 months. The animals gained significant body weight (body mass index increased from 30.5 +/- 0.5 to 35.7 +/- 2.8 kg/m2) and skinfold parameters of body fat increased as well. Total cholesterol increased from 109 +/- 4 to 390 +/- 25 mg/dl (P < 0.001), and there were also significant increases in LDL- and HDL-cholesterol and triglyceride. While there was very little relationship between body fat and plasma lipids before the diet, after 12 months, there were significant negative correlations between total and LDL-cholesterol and anthropometric measures of body fat (r ranged from -0.37 to -0.55, P < 0.01). The correlations were not affected when the effects of baseline body mass index and serum cholesterol and total food intake were controlled by partial correlation analysis. In this sample of animals, the acquisition of greater body fat appeared to protect against rises in cholesterol in response to consumption of a high-fat cholesterol-containing diet.
Exp Mol Pathol 1993 Feb
PMID:Body fat and fat distribution by anthropometry and the response to high-fat cholesterol-containing diet in monkeys. 845 36

Total blood and plasma free amino acids and plasma urea levels were studied in fed and 24 h fasted Zucker rats. In fed animals there were no differences between obese and lean rats in the overall essential and non essential blood free amino acids. However, starvation reduced blood amino acid levels in the obese animals compared to the lean group, mainly due to changes in the plasma compartment. The reduction of available amino acids from plasma in the obese rats during starvation affected most of the amino acids, including the branched chain amino acids, which showed higher levels in the fed situation than in lean rats. Of particular interest is the opposite response to starvation in lean and obese Zucker rats concerning the plasma ratio of tryptophan (Trp) to the large neutral amino acids (LNAA) which could be implicated in the alteration of food intake and energy expenditure characteristic of obesity.
Biochem Mol Biol Int 1993 Mar
PMID:Opposite response to starvation of Trp/LNAA ratio in lean and obese Zucker rats. 848 65


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