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)

The effects of cafeteria diet-induced obesity upon in vitro uptake of L-Alanine, Glycine, L-Lysine, L-Glutamine, L-Glutamic acid, L-Phenylalanine and L-Leucine by isolated rat erythrocytes have been studied. The total Phe and Leu uptakes followed Michaelis-Menten kinetics. The Glu uptake was fitted to diffusion kinetics. The uptakes of Ala, Gly, Lys and Gln were best explained by a two-component transport: one saturable and one diffusion. Obesity increased the Km value for Ala, Gln and Leu, and the Vmax value for Ala, but decreased the Vmax for Lys. Kinetic parameters of Phe uptake were unaffected by obesity. In addition, the pseudo-first order rate constant (Vmax/Km) for Ala, Gly, Gln, Lys and Leu uptake decreased as a result of cafeteria diet-induced obesity. The Kd value for Ala, Gly, Gln and Glu decreased and that of Lys increased as result of obesity. These adaptations could, at least in part, explain alterations in amino acid distribution between blood cells and plasma related to overfeeding or obesity.
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PMID:Effect of diet-induced obesity on kinetic parameters of amino acid uptake by rat erythrocytes. 148 91

An increased aspartate transaminase in the liver of dietary (post-cafeteria) obese rats was found. It was consistent with the functionality of the malate-aspartate shuttle, that could be responsible for enhancement of metabolic efficiency. The muscle and intestine of obese rats showed a greater capacity for alanine and glutamine synthesis than the controls. Furthermore, enterocyte adaptations in the obese rats indicated higher capabilities for the intake of nitrogen than in the controls. In conclusion, the pattern of amino-acid enzyme activities reflected adaptations to keep from amino nitrogen depletion in dietary obesity which were compatible with an enhancement of the metabolic efficiency.
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PMID:Dietary obesity shows adaptations of amino-acid metabolism on enzyme activities to save amino nitrogen. 168 27

The "in vivo" handling of L-alanine in 24 hours starved rats, in which obesity was induced by feeding with cafeteria diet, was compared with that of starved control rats. 14C-alanine was administered in trace amounts in order not to affect the normal handling of this amino acid. The results obtained in blood and liver support a lowered glucose formation from alanine. The specific radioactivities corresponding to lactate, glutamate + glutamine and asparagine as well as total protein and total lipid, were all lowered in the obese group. This strongly suggests that glucose formation from alanine in the liver was impaired. The specific radioactivity of the metabolites studied in the striated muscle are compatible with the above suggestion. It can be concluded that the glucose alanine cycle operation is inhibited in the cafeteria diet starved obese rats.
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PMID:In vivo C14-L-alanine metabolism in rat dietary obesity induced by cafeteria diet. 231 16

A random sample of 290 white men was examined for association between restriction fragment length polymorphism (RFLP) haplotypes (closely linked RFLPs on a single chromosome) of the apolipoprotein-B gene and serum levels of cholesterol, triglyceride, and high-density lipoprotein, obesity, smoking, alcohol consumption, and coronary heart disease. Haplotype or single RFLP frequencies differed significantly for obesity (p less than 0.005), serum cholesterol (p less than 0.005), and coronary heart disease (p less than 0.05), but for no other variable. Obesity was associated with haplotypes involving minimum PvuII and XbaI RFLPs are likely to be in linkage disequilibrium with nearby functional variation predisposing to obesity. Significant variation in serum cholesterol levels was associated with three functional alleles defined by MspI and EcoRI RFLP pairs (p less than 0.03). These RFLPs correspond to charged aminoacid variants at positions 3611 (arginine to glutamine) and 4154 (glutamic acid to lysine), which lie near the low-density-lipoprotein (LDL) receptor binding region of apolipoprotein-B. The three alleles showed stratification of serum cholesterol between low, normal, and high levels. Coronary heart disease was associated with minimum haplotypes involving XbaI and MspI RFLPs. Together these results suggest that inherited variations of the apolipoprotein-B gene, probably in the form of charged aminoacid substitutions, influence circulating cholesterol concentration, and that these and other functional variants of the apolipoprotein-B gene affect susceptibility to coronary heart disease and obesity.
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PMID:Variation of apolipoprotein-B gene is associated with obesity, high blood cholesterol levels, and increased risk of coronary heart disease. 290 69

The obese (ob) gene has been identified through a positional cloning approach; the mutation of this gene causes marked hereditary obesity and diabetes mellitus in mice. We report here the isolation and characterization of the human ob gene. Southern blot analysis demonstrated a single copy of the ob gene in the human genome. The human ob gene spanned approximately 20 kilobases (kb) and contained three exons separated by two introns. The first intron, approximately 10.6 kb in size, occurred in the 5'-untranslated region, 29 base pair (bp) upstream of the ATG start codon. The second intron of 2.3 kb in size was located at glutamine +49. By rapid amplification of 5'-cDNA ends, the transcription initiation sites were mapped 54-57 bp upstream of the ATG start codon. The 172-bp 5'-flanking region of the human ob gene contained a TATA box-like sequence and several cis-acting regulatory elements (three copies of GC boxes, an AP-2-binding site, and a CCAAT/enhancer-binding protein-binding site). By the fluorescence in situ hybridization technique, the ob gene was assigned to human chromosome 7q31.3. This study should establish the genetic basis for ob gene research in humans, thereby leading to the better understanding of the molecular mechanisms underlying the ob gene.
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PMID:Structural organization and chromosomal assignment of the human obese gene. 749 40

Membrane vesicles from the small intestine brush border were obtained and used to determine the possible effects of genetic or nutritional obesity on L-alanine uptake. Membrane vesicles from Zucker fa/fa obese rats and cafeteria diet-fed Zucker Fa/? rats showed the same characteristics as those of standard diet-fed lean animals. All preparations showed sodium-dependent transport as the main pathway for L-alanine uptake within the substrate concentration range tested. The apparent substrate affinity constant (Km) values and the pattern of inhibition of Na(+)-dependent L-alanine uptake by other amino acids (L-leucine and L-glutamine), suggests that system B involved in the transport of dipolar amino acids (formerly named Neutral Brush Border System) participates in the Na(+)-dependent transport of L-alanine. The affinity constant (Km) for L-alanine was essentially the same for all the groups studied (in the range of 10 mM). However, there was a higher (P < 0.05) maximal capacity (Vmax) in preparations from diet-induced obese animals (cafeteria diet) than that of genetically obese rats. These results indicate that either nutritional or genetic obesity may modify the capacity but not the affinity of transport systems for L-alanine uptake in the brush border of rat small intestine.
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PMID:L-alanine transport in small intestine brush-border membrane vesicles of obese rats. 801 96

We have identified a hitherto unrecognized mutation of the lipoprotein lipase gene (LPL) in a Finnish family with Russian and Swiss ancestors. A single base pair substitution of a guanine for cytosine in codon 183 of exon 5 of the LPL gene results in a change of histidine to glutamine in the mature enzyme protein. Expression of a mutant cDNA construct in COS cells resulted in secretion of inactive LPL enzyme protein confirming the functional significance of the mutation. The proband, a 50-year-old female and her two daughters were all heterozygous for the His183-->Gln mutation. Clinically, the proband was characterized by variable and occasionally severe hypertriglyceridemia, obesity, hypertension, coronary heart disease and non-insulin-dependent diabetes mellitus. The daughters, aged 24 and 19 years, were also obese but had milder hypertriglyceridemia. In conclusion, we have identified a novel LPL mutation that results in the synthesis of an inactive enzyme protein. Although the assessment of a causative link between the mutation and hyperlipidemia awaits further studies, our data suggest that heterozygosity for a functional defect of LPL should be considered in patients presenting with the metabolic dyslipidemic syndrome, "syndrome-X."
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PMID:A novel amino acid substitution (His183-->Gln) in exon 5 of the lipoprotein lipase gene results in loss of catalytic activity: phenotypic expression of the mutant gene in a heterozygous state. 816 25

In the present study mRNA from the subcutaneous adipose tissue of 68 obese (defined as a body mass index > or = 27.3 for men and > or = 27.8 for women) and 38 lean subjects was screened for mutations in the ob gene coding region. No mutations in the coding region of the human ob gene were detected using Conformation Sensitive Gel Electrophoresis in 105 subjects. A first base substitution (G to A) was detected in one individual, which changed a valine to a methionine at position 94. The mRNA of all subjects contained the codon for glutamine-49, ruling out the possibility of a splice defect occurring during the removal of intron 2. These observations suggest that defects in the ob gene sequence itself are not the primary cause of obesity in humans.
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PMID:Mutation screening and identification of a sequence variation in the human ob gene coding region. 860 34

The massive obesity caused in rodents by the disruption of the leptin-receptor signal through genetic defects at the level of either leptin (OB) or leptin receptor (OB-R) has raised the question of the relevance of these genes to morbid obesity in humans. In this study, we screened a large population of massively obese subjects for the presence of a leptin receptor mutation homologous to that of fa/fa rats, a single base substitution changing glutamine 269, a highly conserved glutamine found at position 270 in the human sequence. After polymerase chain reaction (PCR) amplification of a DNA region encompassing the end of exon 5, intron 5, and the beginning of exon 6, we performed restriction fragment length polymorphism analysis. Within the limitations of this approach where only mutations introducing restriction sites (5 of 8 possibilities) could be assessed, no evidence of mutation at the codon gln 270 was found in 343 massively obese subjects. However, a new OB-R gene variant in intron 5 was revealed by MaeII digestion of the PCR products. MaeII/hOB-R genotyping revealed no difference in the distribution of the genotypes between obese subjects and a group of 79 unrelated nonobese control subjects. In addition, no significant association between various obesity-related metabolic phenotypes and the presence of MaeII/hOB-R alleles was found. Thus, our results did not support a significant role for the MaeII/hOB-R gene variant in the development of the obese phenotype in the population we studied.
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PMID:Leptin receptor gene in a large cohort of massively obese subjects: no indication of the fa/fa rat mutation. Detection of an intronic variant with no association with obesity. 954 18

The prevaleance of morbid obesity (body mass index of 35.0 or greater) is low in Japan (0.2-0.3%), and little systematic investigation of its cause in this population has been carried out. Leptin plays a central role in regulation of body weight; mice deficient in leptin develop marked obesity. We sought mutations in the leptin gene in 53 morbidly obese Japanese (maximum body mass index 35-60) including 46 with type 2 diabetes. Direct DNA sequencing was performed following polymerase chain reaction amplification. Apart from a silent mutation at codon 25 (CAA/CAG, glutamine) detected in eight subjects, no mutations were detected. We found a significantly higher prevalence of the variant leptin 25CAG allele among the 53 obese subjects (0.085) studied than in 132 nonobese control subjects (0.011, P<0.001). In Japanese populations mutations in the protein coding sequence of the leptin gene are unlikely to be a major cause of morbid obesity. However, the leptin 25CAG allele may be linked to morbid obesity in this population. Specifically, genetic variation located near the leptin gene may be involved in pathogenesis. The leptin polymorphism 25CAG appears to be a new genetic marker for obesity susceptibility, at least in Japanese.
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PMID:A polymorphic marker in the leptin gene associated with Japanese morbid obesity. 1114 Mar 77


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