Association of 5-HT2C (rs3813929) and UCP3 (rs1800849) gene polymorphisms with type 2 diabetes in obese women candidates for bariatric surgery

ABSTRACT Objective Obesity can cause systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) factor that is also influenced by genetic variability. The present study aims to investigate the association between gene polymorphisms related with obesity on the prevalence of SAH and DM2 in the preoperative period and 1 year after Roux-en-Y gastric bypass surgery. Subjects and methods In total, 351 obese women in a Brazilian cohort completed the study. The clinical diagnosis of SAH and DM2 was monitored from medical records. Twelve gene polymorphisms (rs26802; rs572169; rs7799039; rs1137101; rs3813929; rs659366; rs660339; rs1800849; rs7498665; rs35874116; rs9701796; and rs9939609) were determined using real-time polymerase chain reaction and TaqMan assay. Results In the preoperative period, prevalence of SAH and DM2 was 57% and 22%, respectively. One year postoperatively, 86.8% subjects had remission of DM2 and 99.5% had control of SAH. Subjects with T allele from the serotonin receptor gene (5-HT2C, rs3813929) had five times greater chance of DM2, and the CC genotype from uncoupling protein 3 gene (UCP3, rs1800849) had three times greater chance in the preoperative period. Conclusion These findings indicate that polymorphisms rs3813929 and rs1800849 from 5-HT2C and UCP3 genes were related to DM2 prevalence among the Brazilian obese women candidates for bariatric surgery.

Effects of repeated fasting/refeeding on lipid metabolism and uncoupling proteins expression in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the expression changes of mRNA and protein of uncoupling protein 2 (UCP2) in adipose tissues and uncoupling protein 3 (UCP3) in muscle tissues of rats which were treated with repeated fasting/refeeding and followed by fed with high-fat diet, and their possible mechanism on lipid metabolism.</p><p><b>METHODS</b>The model of repeating fasting/refeeding rats (repeated cycles of 1-day fasting and 1-day refeeding for 6 weeks fed with common-fat diet, RFR) was designed. At the end of the 6th week, the RFR rats were switched to high-fat diet every day (RFR-CF/HF). Moreover, the control rats were randomly divided into two groups and then fed with high-fat diet (HF) and common-fat diet (CF) respectively for 6 weeks. All rats were killed at the end of the 6th and the 12th week, serum and plasma samples were taken from abdominal aorta, and then the concentration of serum lipids, glucose, free fatty acid (FFA), and plasma insulin were measured. The histomorphological changes of liver tissues were observed by HE staining. The expression level of mRNA and protein of UCP2 in adipose tissues and UCP3 in muscle tissues was respectively measured by RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) The concentration of serum glucose in RFR group was significantly lower than that in control group (P < 0.05), while the concentration of serum FFA, expression level of UCP2 mRNA, UCP3 mRNA and protein were significantly higher than those in control group (P < 0.05). (2) The concentration of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and plasma insulin in RFR-CF/HF group was significantly lower than that in HF group, but significantly higher than that in CF group (P < 0.05). The concentration of serum FFA was significantly lower than that of HF and CF groups (P < 0.01). The expression level in UCP2, UCP3 mRNA and protein was significantly higher than that of HF group, but significantly lower than that of CF group (P < 0.05).</p><p><b>CONCLUSION</b>The feeding pattern of repeated fasting/refeeding can decrease the obese degree induced by high-fat diet, increase the mRNA and protein expression of UCP2 in adipose tissues and UCP3 in muscle tissues, up-regulate the proton leak caused by obesity, and improve the rate of basic energy metabolism in rats.</p>

Role of astacene in mice skeletal muscle and muscle cell mRNA expression of energy metabolism-related genes / 生物工程学报

In order to examine the role of astacene on mice body development and the expression of energy metabolism related genes in mice, we treated mice (Kunming white) and primary culture of mouse muscle cells with astacene of higher and lower concentration. Then the total mRNA was extracted from the muscle tissue and cells respectively, and the mRNA levels of UCP3 and LXRalpha were detected by RT-PCR in all the samples. Compared with the control group, the body weight of mice in high concentrations of astacene group grown slowly, and the expressions of UCP3 genes decreased significantly in muscle tissue of the 10th day and the 30th day as well as the cells of treated for 24 h (P<0.05). The expression of LXRalpha gene increased significantly in all samples (P<0.05) and reached its peak at 72 h (P<0.01). With the treatment of lower concentration of astacene, the expressions of UCP3 and LXRalpha gene mRNA in muscle tissue did not alter much, but in muscle cells treated for 24 h, the mRNA level of UCP3 gene decreased significantly (P<0.05), and LXRalpha gene increased significantly (P<0.05). The results suggest that astacene has a role in regulating the energy use in mice muscle.

Endurance training attenuates the bioenergetics alterations of rat skeletal muscle mitochondria submitted to acute hypoxia: role of ROS and UCP3 / 生理学报

The physiological significance of skeletal muscle mitochondrial uncoupling protein 3 (UCP3) in hypoxia is elusive. In the current study, UCP3 mRNA and protein expressions were investigated along with mitochondrial respiratory function, reactive oxygen species (ROS) generation, as well as manganese superoxide dismutase (MnSOD) expression in rat skeletal muscle with or without endurance training after an acute and severe hypobaric hypoxia exposure for different time. Acute hypoxia induced a series of impairments in skeletal muscle mitochondrial bioenergetics. In untrained rats, UCP3 protein content increased by 60% above resting level at 4 h hypoxia, whereas MnSOD protein content and activity were unaltered. UCP3 upregulation increased mitochondrial uncoupling respiration thus reducing O2(.-) generation, but inevitably decreased ATP production. Training decreased acute hypoxia-induced upregulation of UCP3 protein (67% vs 42%) in rat skeletal muscle. ROS production in trained rats also showed a dramatic decrease at 2 h, 4 h and 6 h, respectively, compared with that in untrained rats. MnSOD protein contents and activities were significantly (50% and 34%) higher in trained than those in untrained rats. Training adaptation of MnSOD may enhance the mitochondrial tolerance to ROS production, and reduce UCP3 activation during severe hypoxia, thus maintaining the efficiency of oxidative phosphorylation. In trained rats, mitochondrial respiratory control (RCR) and P/O ratios were maintained relatively constant despite severe hypoxia, whereas in untrained rats RCR and P/O ratios were significantly decreased. These results indicate that (1) UCP3 mRNA and protein expression in rat skeletal muscle are upregulated during acute and severe hypobaric hypoxia, which may reduce the increased cross-membrane potential (Deltapsi) and thus ROS production; (2) Endurance training can blunt hypoxia-induced UCP3 upregulation, and improve mitochondrial efficiency of oxidative phosphorylation due to increased removal of ROS.

Effects of maternal high protein diet on uncoupling protein and carnitine palmityl transferase 1 in offspring of rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of maternal nutritional manipulation on fetal mRNA abundance of uncoupling protein UCP2, UCP3 and carnitine palmityl transferase 1 (CPT1), and find out an optimal maternal diet and targets for pharmacological prevention and treatment of obesity.</p><p><b>METHODS</b>Wistar pregnant rats were assigned to two groups which received a standard diet (SD) and a high protein diet (HPD) during pregnancy, respectively. After delivery, the male offspring were assigned to control group (CON) and high protein group (HP) according to their maternal diet, which were suckled by dams that received SD during pregnancy. Offspring were fed with SD from weaning (week 3) to week 8. Then CON were allocated to two groups: CON (SD during the whole experiment); HFCON (high fat control). HFCON and HP group rats were fed with high-fat diet (HFD) for 6 wk to induce obesity. At 0, 3, 8 and 14 wk of age, blood and tissue were collected for analyzing blood fat and abundance of UCP2, 3 and CPT1 mRNA.</p><p><b>RESULTS</b>In HP body weight and TG were decreased after weaning (F = 4.589, P = 0.039; F = 27.001, P = 0.000) and HFD (F = 16.076, P = 0.00; F = 71.518, P = 0.000). Obesity rates were significantly decreased in HP after HFD (chi2 = 8.076, P = 0.004). The abundance of UCP3 and CPT1 mRNA was persistently higher in HP than in CON or HFCON, and the abundance of UCP2 mRNA was also persistently higher than in CON or HFCON after weaning. Moreover the abundance of CPT1 mRNA was significantly increased after weaning and HFD compared with that after SD, the abundance of UCP2, UCP3 mRNA was also increased after HFD compared with that after SD.</p><p><b>CONCLUSIONS</b>Increasing protein intake during pregnancy might prevent offspring from HFD-induced obesity in adult, moreover might increase offspring the expression of UCP2, UCP3 and CPT1 mRNA. UCP2, UCP3 and CPT1 might participate in prevention and treatment of obesity by mediating fatty acid oxidation.</p>

Effect of polymorphism of uncoupling protein 3 gene -55 (C>T) on the resting energy expenditure, total body fat and regional body fat in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of the C to T variant at the -55 site of the promoter region of uncoupling protein 3 gene (UCP3) with the resting energy expenditure and the parameters of body fat in Chinese population.</p><p><b>METHODS</b>Three hundred Chinese (91 normal weight subjects, 209 overweight/obesity subjects) were genotyped for the UCP3 gene -55(C>T) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Resting energy expenditure (REE), fat mass (FM), fat free mass (FFM) and the parameters for regional adipose tissue distribution were measured.</p><p><b>RESULTS</b>Genotype frequencies of UCP3 gene -55(C>T) were not associated with obesity and different types of obesity. The REE level in normal weight subjects with TT homozygotes was higher than that in those with CT heterozygotes and CC homozygotes (P=0.0200). Similar tendency was also observed in overweight/obesity subjects. The FM/FFM exhibited significant difference between the overweight/obesity subjects with a TT genotype and those with a CT or CC genotype (P=0.0096).</p><p><b>CONCLUSION</b>The level of difference in REE caused by the polymorphism of promoter region of UCP3 -55(C>T) may play a role in energy metabolism in Chinese.</p>

Changes in uncoupling protein-2, 3 mRNA expression in the scalded rats after escharectomy at different post scalding stages / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the expression of uncoupling protein (UCP)-2, 3 mRNA in skeletal muscle of the scalded rats after escharectomy at different post scalding stages.</p><p><b>METHODS</b>One hundred and twenty Wistar rats were employed in the study, in which 8 served as normal control (C) and 112 were subjected to 30% TBSA 3rd degree scalding and then again, divided into 4 groups. The rats in A group were sacrificed on 8th, 24th, 96th, 120th and 168th post scalding hours (PSHs) without escharectomy. The rats in B group underwent escharectomy at 8 PSH, and those in C group underwent escharectomy at 24 PSH. All the rats in both groups were sacrificed on 96, 120 and 168 PSHs after escharectomy, Escharectomy was performed at 96 PSH in rats of D group, and they were sacrificed on 120 and 168 PSHs after escharectomy. The serum levels of leptin and TNFalpha, and the expression level of UCP2 mRNA were determined at all time points in all groups of rats.</p><p><b>RESULTS</b>(1) The serum levels of leptin in A group were obviously lower than that in C group (P < 0.01) during 24 approximately 168 PSHs, while those in B, C and D groups were much higher than those in A group (P < 0.01) during 24 approximately 168 PSH. (2) The serum TNFalpha levels in A group at all time points were higher than that in control group, while that in B group at all time points were lower than that in A group (P < 0.05 or 0.01), and that in C group at 168 PSH was lower than that in A group (P < 0.05). (3) The UCP2 mRNA expression in skeletal muscle in A group was increased evidently since 8 PSH (P < 0.01), peaking at 24 PSH and lowering thereafter, while that in B and C groups at 168PSH was significantly lower than that in A group at the same time points (0.32 and 0.35 vs 0.71, P < 0.05). The trend of the change in UCP3 mRNA expression in skeletal muscle was similar to that of UCP2.</p><p><b>CONCLUSION</b>The postburn up-regulation of UCP mRNA expression might play important roles in the increase of metabolic rate. Escharectomy during shock stage could lower down the expression of UCP2 and UCP3 mRNA expression, and it could be beneficial by lowering metabolic rate.</p>

Effects of uncoupling protein 3 gene -55 C-->T variant on lipid metabolism, body fat, its distribution and non-insulin-dependent diabetes mellitus in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of UCP3 gene -55 C-->T variant with lipid metabolism, body fat, its distribution and non-insulin-dependent diabetes mellitus(NIDDM) in Chinese.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was used to detect the genotype of UCP3 gene -55 C-->T in a total of 316 Chinese including 165 individuals with normal glucose tolerance(NGT) and 151 patients with type 2 diabetes). MRI was used to detect local body fat; the enzyme method and sulfate-sephadex-manganese precipitation method were used to detect TC and HDL-C, and then LDL-C was calculated with corresponding formula.</p><p><b>RESULTS</b>(1)No difference was seen on comparing allele and genotype frequencies of Chinese with those of Caucasian (P=0.1120 and P=0.0646, respectively), whereas significant difference in these frequencies was seen between Chinese and Pima Indians(P=0.0 105 and P=0.0314, respectively). (2)Stepwise regression analysis revealed that the independent variables to UCP3 gene -55 C-->T were: HDL-C(P= 0.013)and LDL-C(P=0.012) in male NGT subgroup FA(P=0.023) in female NGT subgroup TG(P=0.004)in male DM subgroup, and waist to hip ratio (WHR)(P=0)in female DM subg roup. (3)The allele frequency of DM group was significantly different from that of NGT(P =0.0358). The odd ratio for the T allele carrier with NIDDM was 1.434 (95%CI 1.031-1.995).</p><p><b>CONCLUSION</b>Although UCP3 gene 55 C-->T variant is associated with lipid metabolism, body fat and its distribution in Chinese, the association is dependent on sex and disease status. The variant is also associated with NIDDM in Chinese.</p>