Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0497406 (overweight)
26,365 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Massive overweight is an increasing health problem and underlies several complications which in turn result in premature death. The mechanisms underlying the imbalance between energy intake and energy expenditure, that lead to obesity in humans, are still only partly understood. In rodents, heat generation and the burning of calories by the mitochondrial uncoupling protein 1 (UCP1) are important for metabolic control. However, UCP1 is exclusively expressed in brown fat which is only present in limited amounts in human adults. The recent characterization of two new uncoupling proteins, UCP2 and UCP3, may elucidate potentially important pathways for energy expenditure regulation in man. The aim of this study was to investigate whether obesity is accompanied by aberrations in UCP2 and UCP3 regulation. Expression of these two genes was examined using in situ hybridization in six lean and six obese, but otherwise healthy, men. The UCP2 expression was decreased by 28 % (p = 0.001) in the abdominal muscle of the obese subjects. No differences in UCP3 expression were observed between obese and control subjects, although there was great variation in the expression between subjects. In conclusion, these data suggest an impaired activity of the mitochondrial uncoupling protein UCP2, but probably not UCP3, in obese subjects. This may result in decreased energy expenditure and contribute to the development and maintenance of obesity.
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PMID:Reduced gene expression of UCP2 but not UCP3 in skeletal muscle of human obese subjects. 972 96

Although the rapid increase in the prevalence of obesity in many countries suggests that environmental factors (mainly overeating and physical inactivity) play the most important role in the development of overweight, it is very likely that genetic factors also contribute. It appears that one major gene in combination with one or several minor genes constitute the genetic components behind excess accumulation of body fat in most obese individuals. However, monogenic obesity has been described in a few families due to changes in leptin, leptin receptor, prohormone convertase, pro-opiomelanocortin or melanocortin-4 receptor. None of the monogenic variants is of great importance for common human obesity; the latter genes are unknown so far. Results from genomic scans suggest that major obesity genes are located on chromosomes 2, 10, 11 and 20. Studies of candidate genes indicate that the minor obesity genes control important functions of adipose tissue, and that structural variance in these genes may alter adipose tissue function in a way that promotes obesity. Such genes are beta 2- and beta 3-adrenoceptors, hormone-sensitive lipase, tumour necrosis factor alpha, uncoupling protein-1, low-density lipoprotein receptor, and peroxisome proliferator activator receptor gamma-2. Some of these genes may promote obesity by gene-gene interactions (for example beta 3-adrenoceptors and uncoupling protein-1) or gene-environment interactions (for example beta 2-adrenoceptors and physical activity). Some are important for obesity only among women (for example beta 2- and beta 3-adrenoceptors, low-density lipoprotein receptor and tumour necrosis factor alpha). Few 'non-adipose' genes have so far shown a firm association to common human obesity, which could suggest that the important genes for the development of excess body fat also control adipose tissue function.
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PMID:Obesity--a genetic disease of adipose tissue? 1088 86

The effect of cold exposure, being overweight and their interaction was investigated on the response of uncoupling proteins UCP1, UCP2 and UCP3 and the alpha(2)/beta(3) adrenergic receptor (AR) balance in brown adipose tissue (BAT), as well as the involvement of leptin gene expression in white adipose tissues, in control and overweight male rats of the dietary obesity model known as the post-cafeteria model. UCP1, UCP2 and UCP3 mRNAs were up-regulated by cold, with a synergic effect of cold exposure and being overweight on UCP1 mRNA levels (with the related UCP1 protein response), and with UCP2 mRNA showing a parallel response. Furthermore, the BAT alpha(2)/beta(3) AR ratio was diminished in overweight rats. The results suggest that the UCP1-dependent thermogenic capacity in BAT of post-cafeteria overweight rats has a more sensitive response to cold exposure and that UCP2 and UCP3 could be somehow involved in the thermogenic response but differentially regulated. Moreover, the diminished alpha(2)/beta(3) AR ratio in BAT could be one of the factors involved in the more sensitive response of overweight rats to cold in terms of BAT thermogenesis-related parameters.
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PMID:Synergic effect of overweight and cold on uncoupling proteins expression, a role of alpha(2)/beta(3) adrenergic receptor balance? 1213 67

Weight loss in response to caloric restriction is variable. Because skeletal muscle mitochondrial proton leak may account for a large proportion of resting metabolic rate, we compared proton leak in diet-resistant and diet-responsive overweight women and compared the expression and gene characteristics of uncoupling protein (UCP)2 and UCP3. Of 1,129 overweight women who completed the University of Ottawa Weight Management Clinic program, 353 met compliance criteria and were free of medical conditions that could affect weight loss. Subjects were ranked according to percent body weight loss during the first 6 weeks of a 900-kcal meal replacement protocol. The highest and lowest quintiles of weight loss were defined as diet responsive and diet resistant, respectively. After body weight had been stable for at least 10 weeks, 12 of 70 subjects from each group consented to muscle biopsy and blood sampling for determinations of proton leak, UCP mRNA expression, and genetic studies. Despite similar baseline weight and age, weight loss was 43% greater, mitochondrial proton leak-dependent (state 4) respiration was 51% higher (P = 0.0062), and expression of UCP3 mRNA abundance was 25% greater (P < 0.001) in diet-responsive than in diet-resistant subjects. There were no differences in UCP2 mRNA abundance. None of the known polymorphisms in UCP3 or its 5' flanking sequence were associated with weight loss or UCP3 mRNA abundance. Thus, proton leak and the expression of UCP3 correlate with weight loss success and may be candidates for pharmacological regulation of fat oxidation in obese diet-resistant subjects.
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PMID:Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women. 1214 58

The objective of this study was to investigate the sex-dependent regulation of skeletal muscle uncoupling protein (UCP)3 mRNA expression in response to overweight and its relationship with serum levels of free fatty acids, leptin, and insulin. Two obesity models were used: rats made obese by feeding them with a cafeteria diet for 14 wk, and postcafeteria overweight rats fed a chow diet for 10 wk after consuming the cafeteria diet for 14 wk. The effects of 24-h fasting were studied in postcafeteria rats and their age-matched controls. The cafeteria rats ate a high-fat diet and attained an excess body weight that was higher in females (+59%) than in males (+39%). A trend to higher induction of abdominal muscle UCP3 mRNA in male rats than in females after cafeteria diet was apparent (+116% increase vs. +26% increase). Postcafeteria male but not female rats still showed the tendency to have increased UCP3 mRNA levels relative to their age-matched controls. A linear regression analysis showed a significant positive correlation of the UCP3 mRNA levels with overweight and with serum levels of leptin and insulin in males, but not in females, and no correlation with serum free fatty acid levels. A subsequent correlation analysis and a multiple linear regression analysis showed that overweight was the only parameter actually related to UCP3 mRNA levels in males. Fasting-induced upregulation of muscle UCP3 mRNA levels was higher in males (5- to 7-fold) than in females (3- to 4-fold). Our results point to the existence of sex-associated differences in the control of muscle UCP3 expression in response to overweight and fasting, with an impaired induction in female rats under both conditions. The correlation of abdominal muscle UCP3 mRNA expression with overweight in males could be related to their relative resistance to gain weight after chronic overeating of a cafeteria diet, by the purported role of UCP3 in the regulation of lipid utilization.
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PMID:Positive correlation of skeletal muscle UCP3 mRNA levels with overweight in male, but not in female, rats. 1275 Jan 52

The members of the uncoupling protein family have different purported functions, which can be either directly or indirectly related to the control of body weight. In this sense, a great part of the studies carried out on this topic have been made using male subjects, although different works with male and female subjects have shown important sex-associated differences in the regulation of these proteins; for instance, sex differences have been shown in the cold-, diet- and overweight-induced expression of brown adipose tissue UCP1 and also in the correlation of muscle UCP3 with overweight. In these kinds of studies, models of obesity such as the cafeteria diet feeding and postcafeteria have been very useful. Moreover, sex hormones have been shown to modulate UCP1 expression in brown adipocytes in vitro. All of these sex-dependent differences, as well as sex differences in body weight gain under a hypercaloric diet, could be related to the different respective biological functions of male and female subjects and taking into account the gender effect in future studies on obesity could be of interest.
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PMID:Uncoupling proteins: gender-dependence and their relation to body weight control. 1472 66

Members of the uncoupling protein (UCP) family have different purported functions, which can be either directly or indirectly related to the control of body weight. In this sense, most studies on this topic have been carried out using male subjects, although different works with males and females have shown important sex-associated differences in the regulation of these proteins; for instance, sex differences have been shown in the cold-, diet- and overweight-induced expression of brown adipose tissue UCP1 and also in the correlation of muscle UCP3 with overweight. In these kinds of studies, models of obesity such as cafeteria diet feeding and postcafeteria have been very useful. Moreover, sex hormones have been shown to modulate UCP1 expression in brown adipocytes in vitro. All these sex-dependent differences, as well as sex differences in body weight gain under a hypercaloric diet, could be related to the different respective biological functions of males and females, taking into account the fact that the gender effect in future studies on obesity could be of interest.
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PMID:Uncoupling proteins: gender dependence and their relation to body weight control. 1475 47

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.
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PMID:Analysis of candidate genes in Polish families with obesity. 1520 83

The uncoupling protein (UCP) family has been suggested as a possible determinant affecting obesity risk given their function in the regulation of energy metabolism. In an effort to elucidate the effects of UCP family polymorphisms on obesity phenotypes, we genotyped 10 polymorphisms in UCP2 and UCP3 among overweight female subjects (n=458), and genetic effects on BMI and changes after a very low calorie diet (VLCD) were examined. Analyses of VLCD-induced changes among the subjects who had finished one month-weight control program (n=301) revealed that several polymorphisms in UCP2-3 gene cluster showed associations with changes of BMI and fat mass, however not of protein mass. One of the major haplotypes of UCP2-3 gene cluster, ht1 (GGCdelCGTACC), and UCP2-866G>A showed significant associations with VLCD-induced fat reduction (P=0.002 and 0.004; P(corr)=0.03 and 0.01, respectively), and these results suggested that UCP2-3 polymorphisms were important genetic factor for the VLCD-induced reduction of body fat mass.
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PMID:Effects of genetic polymorphisms of UCP2 and UCP3 on very low calorie diet-induced body fat reduction in Korean female subjects. 1754 66

To investigate the associations of uncoupling protein (UCP)2 and UCP3 gene variants with overweight and related traits, we genotyped UCP2-866G>A, UCP2Ala55Val, and UCP3-55C>T in 737 Korean children and 732 adults and collected data regarding anthropometric status and blood biochemistry. Information concerning the children's lifestyles and dietary habits was collected. The UCP2-866G>A and UCP3-55C>T gene variants showed significant associations with BMI level, waist circumference, and body weight in the children but not in the adults. Compared with -866GG carriers, the -866GA and AA carriers showed a strong decreasing trend in the risk for overweight (odds ratio (OR), 0.67; 95% confidence interval (CI), 0.45-1.01; P = 0.053). In comparison with UCP3-55CC carriers, children carrying -55CT and TT showed a significant reduction in the risk of overweight (OR, 0.67; 95% CI, 0.46-0.98; P = 0.039). There was also evidence of interactions between the effects of the combined UCP2-UCP3 genotype and obesity-related metabolic traits. The greatest protective effect against overweight was seen in those with the combined genotype non-UCP2-866GG and non-UCP3-55CC, as compared with those carrying both UCP2-866GG and UCP3-55CC (OR,0.60; 95% CI, 0.38-0.95; P = 0.030). In the subgroup with a low level of physical activity, UCP3-55CC carriers had higher BMI values than UCP3-55T carriers (16.6 +/- 2.3 kg/m(2) vs. 16.1 +/- 1.9 kg/m(2), P = 0.016). Low physical activity may aggravate the susceptibility to overweight in UCP2-866GG and UCP3-55CC carriers.
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PMID:Effects of UCP2 and UCP3 variants on the manifestation of overweight in Korean children. 1903 13


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