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)

We conducted a survey of 356 married couples and their 552 children living in Hisayama in Fukuoka prefecture in order to investigate the correlation between changes in obesity from adolescence to young adulthood. 1. A positive correlation between couples in weight and height could be found, but its coefficient was weak (r = 0.12, 0.10). There was no correlation between couples in BMI. 2. The correlation between parents and their children in height, weight and BMI was significantly positive (r = 0.18, 0.45), having a coefficient greater than that of the correlation between married couples. 3. The correlation coefficient between mother and child was greater than that of the correlation coefficient between father and child. 4. The BMI of a child with either parent obese was significantly greater than that of a child with neither parent obese. Obesity appeared more frequently in children whose BMI of parent was higher. 5. A positive correlation between the BMI of young adults and that of adolescents could be found, and the average BMI of the obesity group was higher than that of the non-obesity group even in the adolescent subjects. 6. Even after considering BMI during adolescence, the familial factor had a significant relationship to the BMI of young adulthood. These results suggest that obesity in adolescence will influence obesity in young adulthood, and that the appearance of obesity strongly correlates with the familial obesity factor. In conclusion, it is very important to take preventative measures, in cooperation with the family, early in a child's adolescent years in order to avoid obesity in adulthood.
 ...
PMID:[Correlation between changes in obesity from adolescence to young adulthood and family obesity--the results of cross sectional and longitudinal studies]. 213 53

Obesity presents a significant challenge to the general health of affluent nations in terms of the number of people affected, the serious associated maladies and the lack of effective treatments. While common wisdom has held that obesity results from 'gluttony and sloth', a number of studies have indicated physiological causes of underlying the pathogenesis of obesity, with the degree of adiposity having a strong genetic component. Recently, the obese gene in the ob/ob mouse was cloned, along with its human homologue. The specific production of the obese protein by adipose tissue suggested that it may function in a feedback loop from fat tissue to the hypothalamus to control energy intake and/or energy expenditure, and that it may play a role in the pathogenesis of human obesity. In this study we report that obese mRNA expression is elevated in ex vivo omental adipocytes isolated from massively obese humans in the absence of an identifiable mutation. Therefore, we speculate that this increased expression may suggest that the massively obese are insensitive to the putative regulatory function(s) of the obese gene product.
 ...
PMID:Increased obese mRNA expression in omental fat cells from massively obese humans. 758 24

The ob gene encodes a protein that, in mutant form, is associated with obesity and type II diabetes in mice. Sequence analysis has revealed no similarities to other proteins, however, and no clues as to possible functions. The possibility nonetheless remains that ob is functionally or ancestrally related to other proteins, whose sequences are divergent to the point that only a comparison of three-dimensional structures might detect relationship. To explore this possibility, we conduct a 'threading' search of a 3-dimensional structure database, to determine whether the ob protein might adopt a fold similar to any known structure. This search reveals that the ob sequence is compatible, at a significance level of P < 0.05, with structures from the family of helical cytokines that includes interleukin-2 and growth hormone. A structural model of ob based upon these results is physically and biologically plausible and leads to testable predictions, including the prediction that ob may activate the JAK-STAT pathway, via binding to a receptor resembling those of the cytokine family.
 ...
PMID:Threading analysis suggests that the obese gene product may be a helical cytokine. 758 24

The mutant gene responsible for obesity in the ob/ob mouse was recently identified by positional cloning (Zhang Y., R. Proenca, M. Maffel, M. Barone, L. Leopold, and J.M. Friedman. 1994. Nature (Lond.) 372:425). The encoded protein and to represent and "adipostat" signal reflecting the state of energy stores. We confirm that the adipocyte is the source of ob mRNA and that the predicted 16-kD ob protein is present in rodent serum as detected by Western blot. To evaluate the hypothesis that it might represent an adipostat, we assessed serum levels of ob protein and expression of ob mRNA in adipose cells and tissue of rodents in response to a variety of perturbations which effect body fat mass. Both ob protein and ob mRNA expression are markedly increased in obesity. The levels of ob protein are approximately 5-10-fold elevated in serum of db/db mice, in mice with hypothalamic lesions caused by neonatal administration of monosodium glutamate (MSG), and in mice with toxigene induced brown fat ablation, (UCP-DTA). Very parallel changes are observed in adipocyte ob mRNA expression in these models and in ob/ob mice. As predicted however, no serum ob protein could be detected in the ob/ob mice. By contrast to obesity, starvation of normal rats and mice for 1-3 d markedly suppresses ob mRNA abundance, and this is reversed with refeeding. Similarly, ob protein concentration in normal mice falls to undetectable levels with starvation. In the ob/ob, UCP-DTA and MSG models, overexpression of ob mRNA is reversed by caloric restriction. These data support the hypothesis that expression of ob mRNA and protein are regulated as a function of energy stores, and that ob serves as a circulating feedback signal to sites involved in regulation of energy homeostasis.
 ...
PMID:Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. 765 36

The obese (ob) gene, the mutation of which results in severe hereditary obesity and diabetes in mice, has recently been isolated through positional cloning. In this study, we isolated a full-length human ob complementary DNA (cDNA) clone and examined the tissue distribution of ob gene expression in humans. The nucleotide sequences of the human ob cDNA coding region were 83% identical to those of the mouse and rat ob cDNA coding regions. Analysis of the deduced amino acid sequences revealed that the human ob protein is a 166-amino acid polypeptide with a putative signal sequence and is 84 and 83% homologous to the mouse and rat ob proteins, respectively. Northern blot analysis using the cloned human ob cDNA fragment as a probe identified a single messenger RNA (mRNA) species 4.5 kb in size found abundantly in the adipose tissues obtained from the subcutaneous, omental, retroperitoneal, perilymphatic, and mesenteric fat pads. However, no significant amount of ob mRNA was present in the brain, heart, lung, liver, stomach, pancreas, spleen, small intestine, kidney, prostate, testis, colon, or skeletal muscle. The ob mRNA level in the adipose tissue varied from region to region even in the same individual. Furthermore, in the human adipose tissue, ob gene expression occurred in mature adipocytes rather than in stromal-vascular cells. This study is the first report of the elucidation of ob gene expression in human tissues, thereby leading to better understanding of the physiological and clinical implications of the ob gene.
 ...
PMID:Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. 778 54

The mouse obese (ob) gene has recently been isolated through the positional cloning technique and has been proved to result in the obese and NIDDM phenotype in mice when mutated (Nature 372:425-432, 1994). More recently, it has been demonstrated, by experiments with recombinant ob protein, that ob gene product can cause mice, including ob/ob mice, diet-induced obesity mice, and normal mice, to lower their food intake and body weight (Science 269:540-549, 1995). To investigate the genetic and/or environmental influences underlying the development of NIDDM associated with obesity, we isolated and partially sequenced the human obese (OB) gene. The human OB gene isolated in this study encoded 167 amino acids and its open reading frame was revealed to be divided into two parts with an intermediate intron of approximately 2.4 kb. Using the single-strand conformation polymorphism (SSCP) technique, we screened Japanese and Asian Indian subjects for mutations in the protein coding regions of the OB gene. A total of 75 NIDDM patients with obesity (54 Japanese and 21 Asian Indians), 40 NIDDM patients without obesity (34 Japanese and 6 Asian Indians), and 34 Japanese patients with simple obesity showed no abnormal SSCP patterns in either component of the coding sequences. These results suggested that mutations in the coding regions of the OB gene are not likely to be commonly identifiable and that there would likely be a kind of obesity-associated NIDDM not caused by mutations of the OB gene.
 ...
PMID:Human obese gene: molecular screening in Japanese and Asian Indian NIDDM patients associated with obesity. 862 Oct 21

Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn KN, Coppack SW: Insulin resistance, adipose tissue and coronary heart disease. Clin Sci 82:1-8, 1992; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 149:1514-1520, 1989). While family segregation, adoption, and twin studies have indicated that degree of adiposity has a significant genetic component (Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass index of twins who have been reared apart. N Engl J Med 322:1483-1487, 1990; Bouchard C, Despres J-P, Mauriege P: Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14:72-93, 1993), the genes and predisposing mutations remain poorly understood. This is in contrast to several well-defined genetic models for obesity in rodents, particularly the mouse obese (ob) gene, in which loss-of-function mutations cause severe obesity. Recent studies have demonstrated a substantial reduction in body fat when recombinant ob protein (leptin) is administered to mice. To test the relevance of these observations to human obesity, the location of the human homologue (OB) was established by radiation hybrid mapping and eight microsatellite markers spanning the OB gene region (7q3l.3) were genotyped in 101 obese French families. Affected-sib-pair analyses for extreme obesity, defined by BMI >35 kg/m2, revealed suggestive evidence for linkage to three markers located within 2 cM of the OB gene (D7S514, D7S680, and D7S530). The OB gene is therefore a candidate for genetic predisposition to extreme obesity in a subset of these families.
 ...
PMID:Indication for linkage of the human OB gene region with extreme obesity. 862 Oct 24

Hyperinsulinemia. is associated with an overexpression of mRNA for the ob protein leptin in rodent models of genetic obesity, and insulin has been reported to directly stimulate leptin mRNA in rat adipocytes. Human obesity is also associated with increased leptin mRNA as well as plasma levels, but there have been no reports of the effect of insulin on leptin secretion. We, therefore, tested the hypothesis that insulin stimulates leptin secretion in humans. Using a newly developed leptin assay, immunoreactive leptin was measured in fasting and postprandial plasma samples from 27 healthy adults and in samples before and during euglycemic-hyperinsulinemic then stepped hypoglycemic (hourly steps at 85, 75, 65, 55, and 45 mg/dl) clamps from 10 healthy subjects and 11 patients with IDDM. Plasma leptin was correlated (r = 0.84, P = 0.0005) with BMI in obese but not nonobese subjects and with fasting (r = 0.75, P = 0.008) but not postprandial plasma insulin levels. (Leptin levels did not change postprandially.) Euglycemic hyperinsulinemia did not alter leptin levels, nor did hyperinsulinemic hypoglycemia. Thus, because circulating leptin levels are not increased during postprandial hyperinsulinemia or during euglycemic (or hypoglycemic) hyperinsulinemia, we conclude that, at least in the short term, insulin does not increase leptin secretion in humans and that hyperleptinemia in obese individuals is not likely the result of hyperinsulinemia.
 ...
PMID:Plasma leptin and insulin relationships in obese and nonobese humans. 862 Oct 26

ob protein is hypothesized to be a circulating feedback signal in the regulation of energy balance. Obese, overfed rats have high levels of ob mRNA expression and suppressed voluntary food intake, indicating the presence of a potent satiety factor. The objectives of this experiment were to determine whether feeding rats their normal daily intake in three meals, compared with ad libitum feeding, increased ob mRNA expression and to determine the degree of obesity required to stimulate expression of ob mRNA. Rats were fed ad libitum, were tube-fed their normal intake in three meals a day, or were tube-fed twice normal intake, ob mRNA was measured by Northern blot analysis after 0, 2, 7, 14, 21, and 32 d of tube-feeding. After only 2 d ob mRNA was threefold higher in tube-fed animals than in ad libitum controls. By day 21 there was a further increase in ob mRNA expression in overfed rats which were at 130% control weight. These results suggest that a metabolic consequence of meal-feeding increases ob mRNA expression in the absence of increased food intake or weight gain. There is a further increase in ob mRNA expression once significant obesity is established.
 ...
PMID:Early and late stimulation of ob mRNA expression in meal-fed and overfed rats. 862 90

We have cloned the rhesus monkey obese cDNA and have analyzed its expression in monkeys with a wide range of body weights (lean to very obese) and with or without non-insulin-dependent diabetes mellitus to examine the relationship of ob gene expression to obesity and non-insulin-dependent diabetes mellitus. The sequence of monkey ob protein, excluding the signal peptide, showed 91% identity with the human protein. We observed a significant correlation between the level of ob mRNA and body weight. We also found a significant relationship between ob mRNA and fasting plasma insulin concentration; however, insulin stimulation during a 100-140-min euglycemic/hyperinsulinemic clamp did not result in any changes in ob mRNA levels. Circulating levels of the ob gene product leptin were also significantly correlated with body weight. These results show that ob gene expression is related to body weight and is not acutely regulated by insulin.
 ...
PMID:Regulation of obese (ob) mRNA and plasma leptin levels in rhesus monkeys. Effects of insulin, body weight, and non-insulin-dependent diabetes mellitus. 881 Feb 96


1 2 3 Next >>