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Copyright of Feed Industry is the property of Liaoning Provincial Institute of Agricultural Mechanization and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Folia Pomeranae Universitatis Technologiae Stetinensis Agricultura Alimentaria Piscaria et Zootechnica is the property of West Pomeranian University of Technology in Szczecin and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Uncoupling protein 3 (Ucp3) is an important transporter within mitochondria and is mainly expressed in skeletal muscle, brown adipose tissue and the myocardium. However, the effects of Ucp3 on myogenic differentiation are still unclear. This study evaluated the effects of Ucp3 on myogenic differentiation, myofiber type and energy metabolism in C2C12 cells. Gain- and loss-of-function studies revealed that Ucp3 could increase the number of myotubes and promote the myogenic differentiation of C2C12 cells. Furthermore, Ucp3 promoted the expression of the type IIb myofiber marker gene myosin heavy chain 4 (Myh4) and decreased the expression of the type I myofiber marker gene myosin heavy chain 7 (Myh7). In addition, energy metabolism related to the expression of PPARG coactivator 1 alpha (Pgc1-α), ATP synthase, H+ transportation, mitochondrial F1 complex, alpha subunit 1 (Atp5a1), lactate dehydrogenase A (Ldha) and lactate dehydrogenase B (Ldhb) increased with Ucp3 overexpression. Ucp3 could promote the myogenic differentiation of type IIb myotubes and accelerate energy metabolism in C2C12 cells. This study can provide the theoretical basis for understanding the role of Ucp3 in energy metabolism. [ABSTRACT FROM AUTHOR]

Nonsyndromic monogenic obesity (NSMO) is a class of individual obesity that is independent of the environment and caused by a single gene mutation. It is mostly caused by mutations in LEP, LEPR, PCSK1, as well as some rare mutations in UCP3, NR0B2, and PPARG. Among 30 obesity patients, five patients are identified with positive gene detection. For the first time, the c.624C>T mutation associated with PCSK1, and the c.50G>A and c.293_301delinsAC mutations associated with NR0B2, as well as the obesity phenotype mutation (c.284A>G) associated with PPARG is confirmed. Following this, the genotype‐clinical phenotype, mutation hotspots, and mutation distributions of each gene are summarized, and the genetic characteristics of NSMO are analyzed. The locations of mutation c.50G>A, and c.284A>G are highly conserved according to the sequencing alignment. According to the findings, the c.624C>T mutation in PCSK1 is a newly discovered synonymous mutation, but it can result in significant early‐onset obesity. Additionally, the mutation of c.284A>G(PPARG) can lead to a variety of clinical phenotypes and the mutation of UCP3 and NR0B2 may increase the risk of type 2 diabetes mellitus. This study enriches the human NSMO gene mutation database and provides a scientific basis for clinically accurate diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Aim: Vitamin D3 has been implicated in multiple reproductive events, whereas the effect of its bioactive metabolite 1α, 25 dihydroxyvitamin D3 (1,25(OH) 2D3) on transcriptome profile of the placenta is unclear. The aim of this article is to determine transcriptome‐wide profile caused by 1,25(OH) 2D3 in human placental trophoblast cells. Methods: We performed RNA sequencing after stimulation of HTR‐8/SVneo cells with 0.1, 1, 10, and 100 nM 1,25(OH)2D3 for 24 h, identified differentially expressed genes by edgeR package (version 3.38.4), and analyzed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways by webtool Metascape. Also, common genes and specific genes in different concentrations of 1,25(OH) 2D3 were identified. Results: There were 180, 158, 161, and 174 differentially expressed genes after 0.1, 1, 10, and 100 nM 1,25(OH) 2D3 stimulation, respectively. KEGG pathway analysis displayed that "lipid and atherosclerosis" were significantly enriched at 0.1 and 1 nM 1,25(OH)2D3, while "cytokine‐cytokine receptor interaction," "TGF‐beta signaling pathway" and "hippo signaling pathway" were significantly enriched in 1, 10, and 100 nM 1,25(OH)2D3. CYP24A1 was a significantly expressed common gene. UCP3 was significantly expressed in low concentrations and might affect energy metabolism. TCF24, EIF3CL, ABCD2, EPHA7, CRLF1, and SECTM1 were specific genes at physiological concentration. Similarly, SPDYE1, IQUB, IL18R1, and ZNF713 were considered as specific genes at supraphysiological concentration. Conclusions: 1,25(OH)2D3 mainly affected the expression of CYP24A1 gene in HTR‐8/SVneo cells. Specific genes accounted for the majority of differentially expressed genes at different concentrations. However, their functions need to be further confirmed. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Northwest A & F University - Natural Science Edition is the property of Editorial Department of Journal of Northwest A&F University (Natural Science Edition) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Currently, it is known that irisin can participate in the processes of thermoregulation and browning of adipose tissue, and, therefore, it is possible that it is involved in the microevolutionary mechanisms of adaptation to a cold. The aim of this study is to investigate the relationship between the uncoupling protein genes (UCP1, UCP2, UCP3) and the irisin levels in the residents of the coldest region of Siberia. The sample consisted of 279 Yakut people (185 females, 94 males, average age 19.8 ± 2.03 years). The females plasma irisin concentration was 8.33 ± 2.74 mcg/mL and the males was 7.76 ± 1.86 mcg/mL. Comparative analysis of irisin levels with the genotypes of six studied SNP-markers in females revealed a significant association of irisin with rs1800849-UCP3. The TT genotype of rs1800849 was associated with elevated levels of irisin (p = 0.01). It was also found that this TT genotype in females was associated with reduced weight and height (p = 0.03). We searched for natural selection signals for the T-allele rs1800849-UCP3; as a result of which, it was found that this allele has a significantly high frequency of distribution in northern (45%, CI: 0.42–0.484) compared with southern Asian populations (28%, CI: 0.244–0.316) (p = 0.01). The results obtained indicate the probable involvement of irisin and the UCP3 gene in thermoregulation, and the spread of its allelic variants is probably related to adaptation to a cold climate. [ABSTRACT FROM AUTHOR]

Background: Meteorin-like hormone (Metrnl) is a peptide secreted from the adipose tissue and modulates the whole-body energy metabolism. Metrnl release into the circulation is influenced by obesity, cold exposure, and exercise. Thyroid hormones also exert many of their effects on metabolism through uncoupling proteins (UCPs). This study aimed to determine effect of Metrnl on hypothalamo–hypophysier–thyroid axis and energy metabolism and reveal the possible involvement of UCPs in this process. Methods and results: Fourty male Sprague–Dawley rats were divided into 4 groups with 10 animals in each group: control, sham, 10 and 100 nM Metrnl. Hypothalamus, muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) samples were collected to detect thyrotropin-releasing hormone (TRH), and UCP1 and UCP3 protein levels by western blot analysis. Serum thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) hormone levels were determined by enzyme-linked immunosorbent assay. Central infusion of Metrnl caused significant increase in serum TSH, T3 and T4 levels compared to control (p < 0.05). After Metrnl treatment, there were significant increases in TRH in hypothalamus tissue, UCP1 in WAT and BAT; and UCP3 protein in the muscle tissue (p < 0.05). Conclusions: The findings that Metrnl induced increases in the peripheral UCPs and hypothalamus–pituitary–thyroid axis hormones implicate a role for this hormone in body energy homeostasis through UCP-mediated mechanisms. [ABSTRACT FROM AUTHOR]

The antioxidant role of mitochondrial uncoupling protein 3 (UCP3) is controversial. This work aimed to investigate the effects of UCP3 on the heart of mice housed at thermoneutral temperature, an experimental condition that avoids the effects of thermoregulation on mitochondrial activity and redox homeostasis, preventing the alterations related to these processes from confusing the results caused by the lack of UCP3. WT and KO UCP3 mice were acclimatized at 30 °C for 4 weeks and hearts were used to evaluate metabolic capacity and redox state. Tissue and mitochondrial respiration, the activities of the mitochondrial complexes, and the protein expression of mitochondrial complexes markers furnished information on mitochondrial functionality. The levels of lipid and protein oxidative damage markers, the activity of antioxidant enzymes, the reactive oxygen species levels, and the susceptibility to in vitro Fe-ascorbate-induced oxidative stress furnished information on redox state. UCP3 ablation reduced tissue and mitochondrial respiratory capacities, not affecting the mitochondrial content. In KO UCP3 mice, the mitochondrial complexes activities were lower than in WT without changes in their content. These effects were accompanied by an increase in the level of oxidative stress markers, ROS content, and in vitro susceptibility to oxidative stress, notwithstanding that the activities of antioxidant enzymes were not affected by UCP3 ablation. Such modifications are also associated with enhanced activation/phosphorylation of EIF2α, a marker of integrated stress response and endoplasmic reticulum stress (GRP778 BIP). The lack of UCP3 makes the heart more prone to oxidative insult by reducing oxygen consumption and increasing ROS. Our results demonstrate that UCP3 helps the cell to preserve mitochondrial function by mitigating oxidative stress. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate whether the anti-diabetic effects of γ-aminobutyric acid (GABA) and insulin can be mediated through the regulation of gene expression related to irisin production and mitochondrial biogenesis in type 2 diabetic mellitus (T2DM) rats. Four groups (n = 6) were used in this study: control, T2DM, T2DM + insulin, and T2DM + GABA groups. After T2DM induction for 3 months (high-fat diet + 35 mg/kg streptozotocin) and treatment with GABA or insulin for 3 months, circulating levels of FBG, triglyceride, LDL, Ox-LDL, and insulin as well as hepatic and serum irisin levels were measured. The mRNA expressions of fibronectin type III domain-containing protein 5 (FNDC5), mitochondrial transcription factor A (TFAM), and mitochondrial uncoupling protein 3 (UCP3) were also evaluated in the skeletal muscle of all groups. GABA therapy improved the FBG and insulin levels in diabetic rats. Insulin treatment significantly reduced FBG and failed to maintain glucose close to the control level. Insulin or GABA therapy significantly decreased the levels of LDL, Ox-LDL, and HOMA-IR index. Circulating irisin levels were markedly decreased in insulin-treated group, while irisin levels did not show significant changes in GABA-treated group compared with control group. GABA or insulin therapy increased mRNA expressions of TFAM and UCP3 in diabetic rats. GABA therapy also led to a significant increase in FNDC5 mRNA. Our findings suggest that the anti-diabetic effect of GABA may be mediated, in part, by a decrease in Ox-LDL levels and an increase in the levels of irisin as well as FNDC5, TFAM, and UCP3 gene expression in T2DM rats. [ABSTRACT FROM AUTHOR]

Background: Hypomagnesemia has been associated with development of type 2 diabetes mellitus (T2DM) and its complications. Irisin has beneficial effects on glucose uptake and improves hepatic glucose and lipid metabolism. In this study, we aimed to evaluate the effects of long-term treatment of MgSO4 and insulin on insulin resistance, dyslipidemia, serum and hepatic irisin levels, skeletal muscle gene expression of fibronectin type III domain-containing protein 5 (FNDC5), mitochondrial transcription factor A (TFAM) and mitochondrial uncoupling protein 3 (UCP3) in T2DM rats. Methods and Results: Twenty-four rats were divided into four groups: Control group, diabetic control (DC) using a high-fat diet + streptozotocin, insulin-treated diabetic group (DC + Ins), MgSO4-treated diabetic group (DC + Mg). At the end of therapies, serum concentrations of FBG, TG, insulin, Ox-LDL, along with serum and hepatic irisin levels were measured. FNDC5, TFAM, and UCP3 mRNA expressions were measured in the skeletal muscle by Real-time PCR. In comparison with DC group, MgSO4 therapy resulted in decreased FBG, TG, Ox-LDL, improved serum insulin and irisin levels, and increased mRNA expressions of FNDC5, UCP3 and TFAM. Insulin therapy significantly decreased FBG, Ox-LDL, FNDC5 and serum irisin levels compared with the control group. While, insulin therapy markedly increased TFAM and UCP3 compared with the DC group. Conclusions: In conclusion, MgSO4 can improve insulin resistance and hyperlipidemia partly through decreasing Ox-LDL, increasing serum irisin levels as well as increasing FNDC5, TFAM, and UCP3 mRNA expressions in T2DM rats. These findings can be considered in the management of diabetes treatment. [ABSTRACT FROM AUTHOR]

Background: We investigated the possible association of uncoupling protein 3 gene (UCP3) single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in nonalcoholic fatty liver disease (NAFLD) Brazilian patients. Methods:UCP3 SNPs rs1726745, rs3781907, and rs11235972 were genotyped in 158 biopsy-proven NAFLD Brazilian patients. Statistics was performed with JMP, R, and SHEsis softwares. Results: The TT genotype of rs1726745 was associated with less occurrence of MetS (P = 0.006) and with lower body mass index (BMI) in the entire NAFLD sample (P = 0.01) and in the NASH group (P = 0.02). The rs1726745-T was associated with lower values of AST (P = 0.001), ALT (P = 0.0002), triglycerides (P = 0.01), and total cholesterol (P = 0.02) in the entire NAFLD sample. Between groups, there were lower values of aminotransferases strictly in individuals with NASH (AST, P = 0.002; ALT, P = 0.0007) and with MetS (AST, P = 0.002; ALT, P = 0.001). The rs3781907-G was associated with lower GGT elevation values in the entire NAFLD sample (P = 0.002), in the NASH group (P = 0.004), and with MetS group (P = 0.003) and with protection for advanced fibrosis (P = 0.01). The rs11235972-A was associated with lower GGT values in the entire NAFLD sample (P = 0.006) and in the NASH group (P = 0.01) and with MetS group (P = 0.005), with fibrosis absence (P = 0.01) and protection for advanced fibrosis (P = 0.01). The TAA haplotype was protective for NASH (P = 0.002), and TGG haplotype was protective for MetS (P = 0.01). Conclusion:UCP3 gene variants were associated with protection against NASH and MetS, in addition to lower values of liver enzymes, lipid profile, BMI and, lesser fibrosis severity in the studied population. [ABSTRACT FROM AUTHOR]

Post-myocardial infarction heart failure (post-MI HF) is one of the leading global causes of death, and current prevention and treatment methods still cannot avoid the increasing incidence. Honokiol (HK) has previously been reported to improve myocardial ischemia/reperfusion injury and reverse myocardial hypertrophy by activating Sirt1 and Sirt3. We suspect that HK may also have a therapeutic effect on post-MI HF. In this study, we aimed to investigate the efficacy and mechanism of HK in the treatment of post-MI HF. We found that HK inhibited myocardial reactive oxygen species (ROS) production, reduced myocardial fibrosis, and improved cardiac function in mice after MI. HK also reduced the abnormality of mitochondrial membrane potential (MMP) and apoptosis of cardiomyocytes caused by peroxide in neonatal cardiomyocytes. RNAseq results revealed that HK restored the transcriptome changes to a certain extent and significantly enhanced the expression of mitochondrial inner membrane uncoupling protein isoform 3 (Ucp3), a protein that inhibits the production of mitochondrial ROS, protects cardiomyocytes, and relieves heart failure after myocardial infarction (MI). In cardiomyocytes with impaired Ucp3 expression, HK cannot protect against the damage caused by peroxide. More importantly, in Ucp3 knockout mice, HK did not change the increase in the ROS level and cardiac function damage after MI. Taken together, our results suggest that HK can increase the expression of the cardioprotective protein Ucp3 and maintain MMP, thereby inhibiting the production of ROS after MI and ameliorating heart failure. [ABSTRACT FROM AUTHOR]

Herein we detected single nucleotide polymorphisms in MEF2B and UCP3 by DNA sequencing and the KASPar technology and analyzed their association with sheep growth traits. Two synonymous mutations, g.1826 C > T and g.10266 G > C, were detected, respectively, and they were found to be significantly associated with sheep growth traits (p < 0.05). In case of MEF2B g.1826 C > T, the average body weight and chest and cannon circumference of sheep with the CC genotype were significantly higher than those of sheep with the CT and TT genotypes (p < 0.05). Moreover, in case of UCP3 g.10266 G > C, the average body weight and chest and cannon circumference of sheep with the GG genotype were significantly higher than those of sheep with the GC and CC genotypes (p < 0.05). Moreover, the average body weight of sheep with the CC/GG genotype was higher compared with those of other genotype combinations. We also assessed MEF2B and UCP3 expression in different sheep tissues, confirming their expression in all examined tissues. To summarize, we believe that the polymorphisms identified in MEF2B and UCP3 can serve as molecular markers for sheep growth traits. [ABSTRACT FROM AUTHOR]

Copyright of Southwest China Journal of Agricultural Sciences is the property of Editorial Department of Southwest China Journal of Agricultural Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Browning of white adipose tissue (WAT) is a promising approach to obesity treatment. During browning, WAT transforms into beige adipose tissue through stimulation of the peroxisome proliferator activated receptor γ (PPARγ). Nutmeg, one of the Indonesian herbs, reportedly has dual roles as a PPARα/γ partial agonist. Even though nutmeg has been traditionally used in body weight reduction, there is limited information regarding the potential role of nutmeg in browning of WAT. Objectives: In this study, we explored the effect of nutmeg seed extract (NuSE) as a potential inductor of WAT browning. Methods: Twelve male Wistar rats, 5–6 weeks old, were divided into control and nutmeg groups. The rats in nutmeg group were given NuSE for 12 weeks by oral gavage. After 12 weeks, the rat's inguinal WAT and brown adipose tissue (BAT) were collected, weighed and stored at − 80°C until use. Results: We observed that even though NuSE did not reduce the final body weight, it significantly reduced body weight gain. NuSE also increased protein levels of peroxisome proliferator activated receptor γ coactivator 1α (PGC‐1α) and uncoupling protein 3 (UCP3) significantly and tended to increase UCP2 and UCP1 levels. Furthermore, NuSE induced macroscopic and microscopic morphological changes of inguinal WAT, marked by significantly increased adipocyte numbers and decreased adipocyte size. Conclusions: Even though NuSE did not increase UCP1 significantly, it potentially alters inguinal WAT characteristics and leads to browning through PGC‐1α and UCP3 induction. However, UCP3's specific mechanism in WAT browning remains unclear. Our findings could contribute to obesity treatment in the future. [ABSTRACT FROM AUTHOR]

Aim: Uncoupling protein 3 (UCP3) has been identified as a type 2 diabetes (T2D) candidate gene and variant rs1800849 is of potential interest as it is present in the regulatory region of UCP3. The aim of the present candidate gene case-control association study was to evaluate the association of variant rs1800849 of UCP3 with T2D in Mizo population from Northeast India. Methodology: The variation was genotyped using TaqMan allele discrimination assay in 767 individuals (425 cases and 342 healthy controls). Results: The variant rs1800849 of UCP3 was not found to be significantly associated with T2D (p-value = 0.733) in studied population group. Conclusion: Thus, it is concluded that the present study could not replicate the association of variant rs1800849 with genetic susceptibility to T2D in the Mizo population group. This absence of association highlights the genetic heterogeneity prevalent in Indian population groups and warrants screening of other T2D candidate genes in Mizo population group. [ABSTRACT FROM AUTHOR]

Alcohol consumption leads to the dysfunction of multiple organs including liver, heart, and skeletal muscle. Alcohol effects on insulin resistance in liver are well evidenced, whereas its effects in skeletal muscle remain controversial. Emerging evidence indicates that alcohol promotes adipose tissue dysfunction, which may induce organ dysregulation. We show that consumption of ethanol (EtOH) reduces the activation of 5′AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) as well as the protein of carnitine palmitoyltransferase 1 (CPT1) and glucose transporter type 4 (GLUT4) in C2C12 myotube. We observed that chronic EtOH consumption increases free fatty acid levels in plasma and triglyceride (TG) accumulation in skeletal muscle and that these increases induce insulin resistance and decrease glucose uptake. Hence, ethanol dysregulates metabolic factors and induces TG accumulation. We found peroxisome proliferator-activated receptor β/δ (PPARδ) activation recovers AMPK activation and increases carnitine-acylcarnitine translocase (CACT) protein. These effects may contribute to enhance mitochondrial activation via uncoupling protein 3 (UCP3) when fatty acids are used as a substrate, thus reduces EtOH-induced increases in TG levels in skeletal muscle. In addition, PPARδ activation recovered EtOH-induced loss of protein kinase B (AKT) phosphorylation at serine 473 via rapamycin-insensitive companion of mammalian target of rapamycin (Rictor) activation. Importantly, PPARδ activation enhanced mitochondrial uncoupling via UCP3. Taken together, the study shows PPARδ enhances fatty acid utilization and uncoupled respiration via UCP3 and protects against EtOH-induced lipotoxicity and insulin resistance in skeletal muscle. [ABSTRACT FROM AUTHOR]

Ovariectomy leads to weight gain primarily in the form of adipose tissue in rodents. The authors investigated whether swimming improves ovariectomy-induced obesity through activation of peroxisome proliferatoractivated receptor α (PPARα) in the skeletal muscle of female ovariectomized (OVX) mice, an animal model of postmenopausal women. Female mice were randomly divided into 3 groups (n = 8/group): a sedentary sham-operated group, a sedentary OVX group, and a swim-trained OVX group. After mice were subjected to swim training or kept sedentary for 6 wk, the authors studied the effects of swimming on not only bodyweight gain, white adipose tissue (WAT) mass, adipocyte size, and skeletal-muscle lipid accumulation but also the expression of skeletal-muscle PPARα target genes. Sedentary OVX mice had significantly higher body weight and WAT than sedentary sham mice. However, swim training reduced body-weight gain, WAT mass, and adipocyte size of OVX mice. Swim-trained OVX mice had significantly lower levels of serum triglycerides and total cholesterol than sedentary OVX mice. Lipid accumulation in skeletal muscle was also markedly decreased by swimming. Concomitantly, swim training significantly increased mRNA levels of skeletal-muscle PPARα and its target enzymes, as well as uncoupling protein 3 (UCP3) responsible for fatty-acid oxidation. These results suggest that swimming can effectively prevent weight gain, adiposity, adipocyte hypertrophy, and lipid disorders caused by ovariectomy, in part through the activation of PPARα and UCP3, in the skeletal muscle of female mice and may contribute to the alleviation of metabolic syndrome, including obesity, hyperlipidemia, and Type 2 diabetes in postmenopausal women. [ABSTRACT FROM AUTHOR]

Key points: We report that the peroxisome proliferator‐activated receptor (PPAR)γ coactivator 1‐α (PGC‐1α)/PPARβ axis is a crucial mediator of uncoupling protein 3 (UCP3) expression in skeletal muscle cells via the transactivativation of a distal PPAR response element at the Ucp3 gene promoter.This mechanism is activated during the myogenic process and by high concentrations of fatty acids independent of PGC‐1α protein levels.Ucp3 is essential for PGC‐1α‐induced oxidative capacity and the adaptive mitochondrial response to fatty acid exposure.These findings provide further evidence for the broad spectrum of the coactivator action in mitochondrial homeostasis, positioning the PGC‐1ɑ/PPARβ axis as an essential component of the molecular regulation of Ucp3 gene in skeletal muscle cells. Uncoupling protein 3 (UCP3) has an essential role in fatty acid metabolism and mitochondrial redox regulation in skeletal muscle. However, the molecular mechanisms involved in the expression of Ucp3 are poorly known. In the present study, we show that the peroxisome proliferator‐activated receptor (PPAR)γ coactivator 1‐α (PGC‐1α)/PPARβ axis is a crucial mediator of Ucp3 expression in skeletal muscle cells. In silico analysis of the UCP3 promoter and quantitative chromatin immunoprecipitation experiments revealed that the induction of the UCP3 transcript is mediated by the transactivation of a distal PPAR response element at the Ucp3 gene promoter by the coactivator PGC‐1α. This mechanism is activated during myogenesis and during metabolic stress induced by fatty acids independent of PGC‐1α protein levels. We also provide evidence that Ucp3 is essential for PGC‐1α‐induced oxidative capacity. Taken together, our results highlight PGC‐1ɑ/PPARβ as an essential component of the molecular regulation of Ucp3 gene in skeletal muscle cells. Key points: We report that the peroxisome proliferator‐activated receptor (PPAR)γ coactivator 1‐α (PGC‐1α)/PPARβ axis is a crucial mediator of uncoupling protein 3 (UCP3) expression in skeletal muscle cells via the transactivativation of a distal PPAR response element at the Ucp3 gene promoter.This mechanism is activated during the myogenic process and by high concentrations of fatty acids independent of PGC‐1α protein levels.Ucp3 is essential for PGC‐1α‐induced oxidative capacity and the adaptive mitochondrial response to fatty acid exposure.These findings provide further evidence for the broad spectrum of the coactivator action in mitochondrial homeostasis, positioning the PGC‐1ɑ/PPARβ axis as an essential component of the molecular regulation of Ucp3 gene in skeletal muscle cells. [ABSTRACT FROM AUTHOR]

Increased fat mass, which is induced by the storage of excess nutrients, is considered a causal factor for various metabolic disorders, including insulin resistance, type 2 diabetes, hyperlipidemia, hyperglycemia, hypertension, atherosclerosis, and non-alcoholic fatty liver disease. Therefore, it is necessary to prevent hyperadiposity to sustain a healthy life. Recently, uncoupling proteins (UCPs) were suggested to be molecular targets for curing obesity and its complications. In this study, green satsuma mandarin orange (Citrus unshiu) extract (GME) increased UCP3 expression in cultured myocytes. In a diet-induced obese animal model, administration of GME reduced fat mass and average fat cell size. Similar to in vitro experiments, GME restored expression of UCP3 in skeletal muscle. Moreover, GME also induced UCP2 expression in skeletal muscle. In conclusion, GME is suggested to be a novel functional dietary supplement for adiposity control through induction of UCPs. [ABSTRACT FROM AUTHOR]

Allelic and genotypic distributions of polymorphisms in the uncoupling protein 3 (UCP3) and forkhead box O1 (FOXO1) genes were assessed in 491 Chinese Qinchuan cattle. Single-locus genotype effects and the combined effect of polymorphisms within those two genes were probed to determine possible association with the carcass quality traits. Using DNA sequencing, in total three novel single nucleotide polymorphisms (SNPs) were identified, including a SNP in the intron 1 of UCP3 (NC_037339.1: g.6821C>T), and two SNPs within the 3'UTR of FOXO1 (NC_037342.1: g.93063G>A and g.93280A>G). Statistical analyses indicated that the g.6821C>T (UCP3) and g.93280A>G (FOXO1) polymorphisms were significantly associated with intramuscular fat content (P < 0.05 or P < 0.01). So, the results obtained in this study constitute a valuable information about the markers applicable in marker-assisted selection (MAS) used in improving carcass quality traits. [ABSTRACT FROM AUTHOR]

This study aims (i) to verify expression of the UCPs, PLIN1, PPARG2, and ADRB3 genes in the abdominal subcutaneous adipose tissue of obese women at baseline and after 8 weeks of supplementation with decaffeinated green tea extract, and (ii) to associate findings with clinical parameters. This is a longitudinal study during which 11 women with obesity grade III were submitted to supplementation with 450 mg of (-)-epigallocatechin gallate (EGCG) (intervention group); the control group consisted of 10 eutrophic women. Anthropometric parameters [weight, height, and body mass index (BMI)], resting metabolic rate (RMR, measured by indirect calorimetry), and gene expression (measured by real-time PCR, RT-qPCR) were determined before and after supplementation. After 8 weeks, clinical parameters and UCP1, PLIN1, PPARG2, and ADRB3 expression remained unaltered in the intervention group (p > .05). Genetic analysis also showed that the UCP3 gene was upregulated (p = .026), but its upregulation did not promote weight loss. [ABSTRACT FROM AUTHOR]

Background/Aims: Many clinical and experimental studies have shown that treatment with statins could prevent myocardial hypertrophy and remodeling induced by hypertension and myocardial infarction. But the molecular mechanism was not clear. We aimed to investigate the beneficial effects of atorvastatin on hypertension-induced myocardial hypertrophy and remodeling in spontaneously hypertensive rats (SHR) with the hope of revealing other potential mechanisms or target pathways to interpret the pleiotropic effects of atorvastatin on myocardial hypertrophy. Methods: The male and age-matched animals were randomly divided into three groups: control group (8 WKY), SHR (8 rats) and intervention group (8 SHR). The SHR in intervention group were administered by oral gavage with atorvastatin (suspension in distilled water, 10 mg/Kg once a day) for 6 weeks, and the other two groups were administered by gavage with equal quantity distilled water. Blood pressure of rats was measured every weeks using a standard tail cuff sphygmomanometer. Left ventricular (LV) dimensions were measured from short-axis views of LV under M-mode tracings using Doppler echocardiograph. Cardiomyocyte apoptosis was assessed by the TUNEL assay. The protein expression of C/EBPβ, PGC-1α and UCP3 were detected by immunohistochemistry or Western blot analysis. Results: At the age of 16 weeks, the mean arterial pressure of rats in three groups were 103.6±6.1, 151.8±12.5 and 159.1±6.2 mmHg respectively, and there wasn’t statistically significant difference between the SHR and intervention groups. Staining with Masson’s trichrome demonstrated that the increased interstitial fibrosis of LV and ventricular remodeling in the SHR group were attenuated by atorvastatin treatment. Echocardiography examination exhibited that SHR with atorvastatin treatment showed an LV wall thickness that was obviously lower than that of water-treated SHR. In hypertrophic myocardium, accompanied by increasing C/EBPβ expression and the percentage of TUNEL-positive cells, the expression of Bcl-2/Bax ratio, PGC-1α and UCP3 were reduced, all of which could be abrogated by treatment with atorvastatin for 6 weeks. Conclusion: This study further confirmed that atorvastatin could attenuate myocardial hypertrophy and remodeling in SHR by inhibiting apoptosis and reversing changes in mitochondrial metabolism. The C/EBPβ/PGC-1α/UCP3 signaling pathway might also be important for elucidating the beneficial pleiotropic effects of atorvastatin on myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

Uncoupling protein 1 (UCP1) is a proton transporter/channel residing on the inner mitochondrial membrane and is involved in cellular heat production. Using immunohistochemistry, we investigated the expression of UCP1 and UCP3 in a series of 98 patients with non-small cell lung cancer (NSCLC) treated with surgery. Expression patterns were correlated with histopathological variables, prognosis, and the expression of enzymes/proteins related to cell metabolism. Bronchial epithelium did not express UCP1 or UCP3, while alveolar cells strongly expressed UCP1. In tumors, strong expression of UCP1 and UCP3 was recorded in 43/98 (43.8%) and 27/98 (27.6%) cases, respectively. UCP1 was significantly associated with squamous cell histology (P = 0.05), whilst UCP3 was more frequently overexpressed in large cell carcinomas (P = 0.08), and was inversely related to necrosis (P = 0.009). In linear regression analysis, UCP1 was directly related to markers of glycolysis [hexokinase (HXKII) and phosphofructokinase (PFK1)] and anaerobic glucose metabolism [pyruvate dehydrogenase kinase (PDK1) and lactate dehydrogenase (LDH5)]. UCP3 was directly linked with a glucose transporter (GLUT2), monocarboxylate transporter (MCT2), glycolysis markers (PFK1 and aldolase), and with the phosphorylation of pyruvate dehydrogenase (pPDH). Kaplan-Meier survival analysis showed that UCP3 was significantly related to poor prognosis in squamous cell carcinomas (P = 0.04). UCP1 and UCP3 are overexpressed in a large subgroup of non-small cell lung tumors and their expression coincides with increased glucose absorption, intensified glycolysis, and anaerobic glucose usage. Whether UCPs are targets for therapeutic interventions in lung cancer is a hypothesis that demands further investigation. [ABSTRACT FROM AUTHOR]

Background: Several lines of evidence revealed that chronic treatment of anabolic androgenic steroids (AASs) is accompanied with some cardiovascular side effects and in addition they also negatively mask the beneficial effects of exercise training on cardiac performance. Methods: The present study examined whether the nandrolone decanoate (ND)-induced cardiac effects were mediated by changing the cardiac uncoupling protein 2 (UCP2) and 3 (UCP3) expression. Five groups of male wistar-albino rats including sedentary control (SC), sedentary vehicle (SV), sedentary nandrolone decanoate (SND), exercise control (EC), and exercise nandrolone decanoate (END) were used. ND was injected (10 mg/kg/week, intramuscular) to the animals in the SND and END groups and endurance exercise training was performed on a treadmill five times per week. Results: The protein expressions of cardiac UCP2 and UCP3 have significantly increased in both the SND and EC groups compared to the SC ones. In contrast to UCP3, no significant differences were found between UCP2 protein expressions of the END and SC groups. Compared with the SND group, the exercise training significantly decreased the UCP2 and UCP3 protein expressions in the END group. Conclusions: The study has indicated that endurance exercise in combination with ND can result in that the exercise effectively antagonizes the effects of ND treatment on UCP2 and UCP3 up-regulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Obesity is linked to high dietary intake and low physical activity. Studies showed that those factors were not only regulated by environment but also regulated by genetic variations. However, the relationship has less been understood in obese children and adolescents. OBJECTIVE: The objective of this study was to examine the role of SNPs (single nucleotide polymorphisms) in uncoupling protein (UCP) 2 -866G/A and UCP3 -55C/T on dietary intake and physical activity in obese female adolescents. METHODS: This is an observational study with cross sectional design. Respondents were obese female adolescents enrolled from obesity screening done in six junior high schools in Yogyakarta. RESULTS: Seventy eight obese female adolescents joined this study. From 2 SNPs that have been analysed, we found that SNPs in UCP2 was associated with dietary intake and physical activity (p = 0.02 and p = 0.02, respectively). Interestingly, subjects with combination of UCP2 -866GG and UCP3 -55CC had slightly higher percent fat to total energy intake compared to those with UCP2 -866AA and UCP3 -55TT (mean difference = -3.8±1.9; p = 0.059). CONCLUSION: We concluded that SNPs on UCP2 was related to dietary intake and physical activity in Indonesian obese female adolescents. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Animal Science is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mitochondrial Ca(2+) uptake (mCa(2+) uptake) is thought to be mediated by the mitochondrial Ca(2+) uniporter (MCU). UCP2 and UCP3 belong to a superfamily of mitochondrial ion transporters. Both proteins are expressed in the inner mitochondrial membrane of the heart. Recently, UCP2 was reported to modulate the function of the cardiac MCU related channel mCa1. However, the possible role of UCP3 in modulating cardiac mCa(2+) uptake via the MCU remains inconclusive. To understand the role of UCP3, we analyzed cardiac mCa1 single-channel activity in mitoplast-attached single-channel recordings from isolated murine cardiac mitoplasts, from adult wild-type controls (WT), and from UCP3 knockout mice (UCP3(-/-)). Single-channel registrations in UCP3(-/-) confirmed a murine voltage-gated Ca(2+) channel, i.e., mCa1, which was inhibited by Ru360. Compared to WT, mCa1 in UCP3(-/-) revealed similar single-channel characteristics. However, in UCP3(-/-) the channel exhibited decreased single-channel activity, which was insensitive to adenosine triphosphate (ATP) inhibition. Our results suggest that beyond UCP2, UCP3 also exhibits regulatory effects on cardiac mCa1/MCU function. Furthermore, we speculate that UCP3 might modulate previously described inhibitory effects of ATP on mCa1/MCU activity as well. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Materials and Methods: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. Results: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. Conclusion: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance. [ABSTRACT FROM AUTHOR]

Several measures have been proposed to investigate and improve feed efficiency in cattle. One of the most commonly used measure of feed efficiency is residual feed intake (RFI), which is estimated as the difference between actual feed intake and expected feed intake based on the animal's average live weight. This measure permits to identify and select the most efficient animals without selecting for higher mature weight. Mitochondrial function has been indicated as a major factor that influences RFI. The analysis of genes involved in mitochondrial function is therefore an alternative to identify molecular markers associated with higher feed efficiency. This study analyzed the expression of PGC1α, TFAM, UCP2 and UCP3 genes by quantitative real-time PCR in liver and muscle tissues of two groups of Nellore cattle divergently ranked on RFI values in order to evaluate the relationship of these genes with RFI. In liver tissue, higher expression of TFAM and UCP2 genes was observed in the negative RFI group. Expression of PGC1α gene did not differ significantly between the two groups, whereas UCP3 gene was not expressed in liver tissue. In muscle tissue, higher expression of TFAM gene was observed in the positive RFI group. Expression of PGC1α, UCP2 and UCP3 genes did not differ significantly between the two groups. These results suggest the use of TFAM and UCP2 as possible candidate gene markers in breeding programs designed to increase the feed efficiency of Nellore cattle. [ABSTRACT FROM AUTHOR]

Background The uncoupling proteins (UCPs) in the mitochondrial inner membrane are members of the mitochondrial anion carrier protein family that play an important role in energy homeostasis. Genetic association studies have shown that human UCP2 and UCP3 variants (SNPs and indels) are associated with obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. The aim of this study was to examine the genetic association between polymorphisms in UCP2 and UCP3 and metabolic data in dogs. Results We identified 10 SNPs (9 intronic and 1 exonic) and 4 indels (intronic) in UCP2, and 13 SNPs (11 intronic and 2 exonic) and one indel (exonic) in UCP3, by DNA sequence analysis of 11 different dog breeds (n = 119). An association study between these UCP2 and UCP3 variants and the biochemical parameters of glucose, total cholesterol, lactate dehydrogenase and triglyceride in Labrador Retrievers (n = 50) showed that none of the UCP2 polymorphisms were significantly associated with the levels of these parameters. However, four UCP3 SNPs (intron 1) were significantly associated with total cholesterol levels. In addition, the allele frequencies of two of the four SNPs associated with higher total cholesterol levels in a breed that is susceptible to hypercholesterolemia (Shetland Sheepdogs, n = 30), compared with the control breed (Shiba, n = 30). Conclusion The results obtained from a limited number of individuals suggest that the UCP3 gene in dogs may be associated with total cholesterol levels. The examination of larger sample sizes and further analysis will lead to increased precision of these results. [ABSTRACT FROM AUTHOR]

Copyright of Revista Latinoamericana de Hipertension is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dietary treatment with high-fat diets (HFD) triggers diabetes and hyperleptinemia, concomitantly with a partial state of leptin resistance that affects hepatic and adipose tissue but not the heart. In this context, characterized by widespread steatosis, cardiac lipid con-tent remains unchanged. As previously reported, HFD-evoked hyperleptinemia could be a pivotal element contributing to increase fatty-acid (FA) metabolism in the heart and to prevent cardiac steatosis. This metabolic adaptation might theoretically reduce energy efficiency in cardiomyocytes and lead to cardiac electrophysiological remodeling. There-fore the aim of the current study has been to investigate the impact of long-term HFD on cardiac metabolism and electrophysiological properties of the principal ionic currents responsible of the action potential duration in mouse cardiomyocytes. Male C57BL/6J mice were fed a control (10 kcal% from fat) or HFD (45 kcal% from fat) during 32 weeks. Quantification of enzymatic activities regulating mitochondrial uptake of pyruvate and FA showed an increase of both carnitine-palmitoyltransferase and citrate synthase activities together with a decrease of lactate dehydrogenase and pyruvate dehydrogenase activities. Increased expression of uncoupling protein-3, Mn-, and Cu/Zn-superoxide dismutases and catalase were also detected. Total glutathione/oxidized glutathione ratios were unaffected by HFD. These data suggest that HFD triggers adaptive mechanisms aimed at (i) facilitating FA catabolism, and (ii) preventing oxidative stress. All these changes did not affect the duration of action potentials in cardiomyocytes and only slightly modified electrocardiographic parameters. [ABSTRACT FROM AUTHOR]

Background: Heat stress down-regulates mitochondrial function, while carbohydrate supplementation attenuates the exercise induced stimulation of mitochondrial biogenesis in humans. The effects of exogenous carbohydrate during exercise in the heat on metabolic mRNA have not been investigated in humans. The purpose of this study was to determine the impact of exercise with and without carbohydrate supplementation on skeletal muscle metabolic response in the heat. Methods: Eight recreationally active males (4.05 ± 0.2 L.min-1) completed 2 trials which included 1 hr of cycling at 70% workload max and 3 hr recovery in a hot environment. Both trials were conducted in a climate controlled environmental chamber (38°C and 40% RH). The trials differed by the consumption of either a 6% carbohydrate (CHO) containing beverage (8 ml.kg-1.hr-1) or placebo (P) during exercise in random order. Muscle biopsies were obtained from the vastus lateralis before exercise, immediately post-exercise and at the end of the 3 hr recovery period. Muscle was analyzed for muscle glycogen and mRNA related to metabolic and mitochondrial development (MFN2, PGC-1α, GLUT4, UCP3). Expired gases were measured to determine whole body substrate use during exercise. Results: Carbohydrate oxidation and muscle glycogen utilization did not differ between trials, whereas fat oxidation was elevated during exercise in P. Exercise caused an increase in PGC-1α, and GLUT4 (P < 0.05) independent of exogenous carbohydrate provision. Carbohydrate consumption attenuated the mRNA response in UCP3 (P < 0.05). Conclusions: This study indicates that the provision of exogenous carbohydrate attenuates the stimulation of mRNA expression of UCP3 following exercise in the heat. [ABSTRACT FROM AUTHOR]

Meat quality traits are economically important traits of swine, and are controlled by multiple genes as complex quantitative traits. In the present study four genes, H- FABP (heart fatty acid-binding protein), MASTR (MEF2 activating motif and SAP domain containing transcriptional regulator), UCP3 (uncoupling protein 3) and MYOD1 (myogenic differentiation 1) were researched in Large White pigs. The polymorphisms H- FABP T/C of 5′UTR, MYOD1 g.257 A>C, UCP3 g.1406 G>A in exon 3 and MASTR c.187 C>T have been reported to be associated with meat quality traits in pigs. The aim of this study was to analyze the effect of single and multiple markers for single traits in Large White pigs. The single marker association analysis showed that the H- FABP and MASTR genes were associated with IMF (intramuscular fat content) ( P < 0.05), and that the g.257 A>C of MYOD1 gene was most significantly related to muscle pH value ( P < 0.01). The multiple markers for IMF were analyzed by combining the markers and quantitative trait modes into the linear regression. The results revealed that H- FABP and MASTR integrate gene networks for IMF. Thus, our study results suggested that H- FABP and MASTR polymorphisms could be used as genetic markers in the marker-assisted selection towards the improvement of IMF in Large White pigs. [ABSTRACT FROM AUTHOR]

This study explores the pharmacokinetics of 22- S-hydroxycholesterol (22SHC) in vivo in rats. We also carried out a metabolic study to explore whether the beneficial effects observed of 22SHC on glucose and lipid metabolism in vitro could be seen in vivo in rats. In the pharmacokinetic study, rats were given 50 mg/kg of [H]22- S-hydroxycholesterol before absorption, distribution and excretion were monitored. In the metabolic study, the effect of 22SHC (30 mg/kg/day for 3 weeks) in rats on body weight gain [chow and high-fat diet (HFD)], serum lipids triacylglycerol (TAG) content and gene expression in liver and skeletal muscle were examined. Results showed that 22SHC was well absorbed after oral administration and distributed to most organs and mainly excreted in feces. Rats receiving 22SHC gained less body weight than their controls regardless whether the animals received chow diet or HFD. Moreover, we observed that animals receiving HFD had elevated levels of serum TAG while this was not observed for animals on HFD supplemented with 22SHC. The amount of TAG in liver was reduced after 22SHC treatment in animals receiving either chow diet or HFD. Gene expression analysis revealed that two genes (carnitine palmitoyltransferase 2 and uncoupling protein 3) involved in fatty acid oxidation and energy dissipation were increased in liver. Ucp3 expression (both protein and mRNA level) was increased in skeletal muscle, but insulin-stimulated glucose uptake and TAG content were unchanged. In conclusion, 22SHC seems to be an interesting model substance in the search of treatments for disorders involving aberrations in lipid metabolism. [ABSTRACT FROM AUTHOR]

Accumulated studies have documented extensive links between UCP3 polymorphisms and pig productive traits, and quantitative trait loci linkage results, on the other hand, provided extensive evidences showing that UCP3 was in the core of several QTLs for carcass and meat quality traits. In this research, we screened two substitutions in coding sequence and one 9-base continuous mutated site in 3′UTR of pig UCP3 gene using the reference population of 293 pigs which were F generation of hybrids between Chinese native Jinhua pigs and European Pietrain. The two missense mutations of G1406A in Exon 3 and T3602C in Exon 5 which led to changes in the G150R and M259T, respectively, were digested by SmaI and introduced Tth111I separately for genotype analysis, and the 9-base continuous mutated site in the 3′UTR was analyzed by an AvaI cleavage. As a result, the 9-base continuous mutated site of 3′UTR manifested significantly close association with the backfat thickness at the sixth and seventh rib, but the polymorphisms of G1406A and T3602C were not associated significantly with any of the seven carcass traits. The same results were shown by RT-qPCR and western blotting. These findings inferred that UCP3 probably has tissue-specific effects on pig carcass traits. [ABSTRACT FROM AUTHOR]

The purpose of this research was to determine the mRNA response to exercise in different environmental temperatures. 9 recreationally active males (27 ± 1 years, 77.4 ± 2.7 kg, 13.5 ± 1.5 % fat, 4.49 ± 0.15 L · min-1 VO2 max) completed 3 trials consisting of 1 h cycling exercise at 60 % Wmax followed by a 3 h recovery in the cold (7°C), room temperature (20°C), and hot (33°C) environments. Muscle biopsies were obtained pre, post, and 3 h post exercise for the analysis of glycogen and mRNA. Expired gases were collected to calculate substrate use. PGC-1α increased to a greater degree in the cold trial than in the room temperature trial (p = 0.036) and the hot trial (p = 0.006). PGC1-α mRNA was also higher after the room temperature trial than the hot trial (p = 0.050). UCP3 and MFN2 mRNA increased with exercise (p < 0.05), but were unaffected by temperature. COX was unaffected by exercise or temperature. Muscle glycogen decreased with exercise (p < 0.05), but was no different among trials. Whole body VO2 was lower during exercise in the cold than exercise in the heat. However, VO2 was higher during recovery in the cold trial than in the room temperature and hot trials (p < 0.05). This study presents evidence of PGC-1α temperature sensitivity in human skeletal muscle. [ABSTRACT FROM AUTHOR]

Abstract: Uncoupling protein 3 (UCP3) may reduce mitochondrial ROS production, and thereby protect against mitochondrial dysfunction in skeletal muscle. UCP3 has been suggested to specifically fulfill this role under high-fat conditions. Here we show that UCP3 knockout mice indeed have elevated mitochondrial ROS production after short-term (8weeks) high-fat feeding. After 26weeks of high-fat feeding, UCP3 knockout mice exhibited reduced mitochondrial function as measured ex vivo in isolated mitochondria. In conclusion, these data suggest that UCP3 may have a role in the protection of mitochondria against lipid-induced mitochondrial dysfunction, but only after long-term exposure to high-fat. [Copyright &y& Elsevier]

Aims/hypothesis: A meta-analysis was performed to assess the association between the UCP2 −866G/A, UCP2 Ala55Val and UCP3 −55C/T polymorphisms and type 2 diabetes susceptibility. Methods: A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further analyses were performed that stratified for ethnicity. Results: We examined 17 publications. Stratified analysis for ethnicity and sensitivity analysis revealed that there was no heterogeneity between studies for these variants. Using an additive model, no significant association of the UCP2 −866G/A polymorphism with type 2 diabetes risk was observed, either in participants of Asian (OR 1.05, 95% CI 0.96, 1.16) or of European (OR 1.03, 95% CI 0.99, 1.07) descent. Neither the UCP2 Ala55Val nor the UCP3 −55C/T polymorphism showed any significant association with type 2 diabetes risk in Europeans (OR 1.04, 95% CI 0.98, 1.09 for Ala55Val; OR 1.04, 95% CI 1.00, 1.09 for −55C/T). In contrast, a statistically significant association was observed for both polymorphisms in participants of Asian descent (OR 1.23, 95% CI 1.12, 1.36 for Ala55Val; OR 1.15, 95% CI 1.03, 1.28 for −55C/T). Conclusions/interpretation: Our meta-analysis suggests that the UCP2 −866G/A polymorphism is unlikely to be associated with increased type 2 diabetes risk in the populations investigated. In contrast, our results indicate that the UCP2 Ala55Val and UCP3 −55C/T polymorphisms may indeed be risk factors for susceptibility to type 2 diabetes in individuals of Asian descent, but not in individuals of European descent. This conclusion warrants confirmation by further studies. [ABSTRACT FROM AUTHOR]

In fission yeast Schizosaccharomyces pombe, the directions of cell growth change from a monopolar manner to a bipolar manner, which is known as 'New End Take Off' (NETO). We previously found that Arf6, a member (class III) of the ADP-ribosylation factor GTPase (Arf) family, is necessary for NETO in fission yeast. Here we report the characterization of a S. pombe gene, ucp3, encoding a putative Arf GTPase-activating protein (GAP) for Arf6. The Ucp3 contains Arf GAP domain, and has a high similarity to Gts1, which was identified as a GAP for Arf3 (class III Arf) in Saccharomyces cerevisiae. Overexpression of ucp3 inhibited growth from new end possibly by disturbing the GDP/GTP-cycling of Arf6. Gene disruption of ucp3 revealed that Ucp3 is essential for cell viability. Ucp3 uniformly localizes to the cell periphery. And its localization is not dependent on microtubules, actin cytoskeletons, Arf6 and Syt22 (guanine nucleotide exchange factor for Arf6). We hypothesize that Ucp3 functions as a GAP for Arf6. Moreover, Ucp3 might have another function important for cell viability. [ABSTRACT FROM AUTHOR]

Pancreatic β-cells have remarkable bioenergetics in which increased glucose supply upregulates the cytosolic ATP/ADP ratio and increases insulin secretion. This arrangement allows glucose-stimulated insulin secretion (GSIS) to be regulated by the coupling efficiency of oxidative phosphorylation. Uncoupling protein 2 (UCP2) modulates coupling efficiency and may regulate GSIS. Initial measurements of GSIS and glucose tolerance in Ucp2−/− mice supported this model, but recent studies show confounding effects of genetic background. Importantly, however, the enhancement of GSIS is robustly recapitulated with acute UCP2 knockdown in INS-1E insulinoma cells. UCP2 protein level in these cells is dynamically regulated, over at least a fourfold concentration range, by rapid proteolysis (half-life less than 1 h) opposing regulated gene transcription and mRNA translation. Degradation is catalysed by the cytosolic proteasome in an unprecedented pathway that is currently known to act only on UCP2 and UCP3. Evidence for proteasomal turnover of UCP2 includes sensitivity of degradation to classic proteasome inhibitors in cells, and reconstitution of degradation in vitro in mitochondria incubated with ubiquitin and the cytosolic 26S proteasome. These dynamic changes in UCP2 content may provide a fine level of control over GSIS in β-cells. [ABSTRACT FROM AUTHOR]

Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles. Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species (ROS) release in skeletal muscle of obese participants with and without type 2 diabetes. Type 2 diabetic men ( n = 13) and control ( n = 14) participants matched for age, BMI and physical activity completed 10 weeks of aerobic training. Pre- and post-training muscle biopsies were obtained before a euglycaemic–hyperinsulinaemic clamp and used for measurement of respiratory function and ROS release in isolated mitochondria. Training significantly increased insulin sensitivity, maximal oxygen consumption and muscle mitochondrial respiration with no difference between groups. When expressed in relation to a marker of mitochondrial density (intrinsic mitochondrial respiration), training resulted in increased mitochondrial ADP-stimulated respiration (with NADH-generating substrates) and decreased respiration without ADP. Intrinsic mitochondrial respiration was not different between groups despite lower insulin sensitivity in type 2 diabetic participants. Mitochondrial ROS release tended to be higher in participants with type 2 diabetes. Aerobic training improves muscle respiration and intrinsic mitochondrial respiration in untrained obese participants with and without type 2 diabetes. These adaptations demonstrate an increased metabolic fitness, but do not seem to be directly related to training-induced changes in insulin sensitivity. [ABSTRACT FROM AUTHOR]

Background:It has been well documented that human adenovirus type 36 (Ad-36) is associated with obesity. However, the underlying molecular mechanism of Ad-36 inducing obesity remains unknown. We sought to investigate the effect of Ad-36 infection on Cidec, AMPK pathway and lipid metabolism in primary cultured human skeletal muscle cells.Methods:Cidec/fat-specific protein 27 (FSP27), fatty acid oxidation, AMPK signaling and the abundance of proteins involved in lipid synthesis were determined in muscle cells infected with various doses (1.9-7.6 MOI) of Ad-36 and non-lipogenic adenovirus type 2 (Ad-2) as a negative control as well as an uninfected control. Cidec/FSP27 siRNA transfection was performed in Ad-36-infected muscle cells.Results:Our data show that Ad-36 significantly reduced fatty acid oxidation in a dose-dependent manner (all P values are <0.01), but Ad-2 did not affect fatty acid oxidation. Ad-36 substantially increased Cidec/FSP27, ACC, sterol regulatory element-binding protein 1c (SREBP-1c), SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase protein abundance, but significantly reduced AMPK activity, mitochondrial mass and uncoupling protein 3 (UCP3) abundance in comparison with control cells (all P values are <0.01). Oil Red O staining revealed that there was substantial fat accumulation in the Ad-36-infected muscle cells. Furthermore, Cidec/FSP27 siRNA transfection significantly reduced FSP27 expression and partially restored AMPK signaling, increased UCP3 and decreased SERBP 1c and perilipin proteins in Ad-36-infected muscle cells. Interestingly, neither Ad-36 nor Ad-2 affected peroxisome proliferator-activated receptor γ protein expression in muscle cells.Conclusion:This study suggests that Ad-36 induced lipid droplets in the cultured skeletal muscle cells and this process may be mediated by promoting Cidec/FSP27 expression. [ABSTRACT FROM AUTHOR]

Uncoupling protein (UCP) 3 is an inner mitochondrial membrane transporter mainly produced in skeletal muscle in humans. UCP3 plays a role in fatty acid metabolism and energy homeostasis and modulates insulin sensitivity. In humans, UCP3 content is higher in fast-twitch glycolytic muscle than in slow-twitch oxidative muscle and is dysregulated in type 2 diabetes. Here, we studied the molecular mechanisms determining human UCP3 levels in skeletal muscle and their regulation by fasting in transgenic mice. We produced a series of transgenic lines with constructs bearing different putative regulatory regions of the human UCP3 gene, including promoter and intron sequences. UCP3 mRNA and reporter gene expression and activity were measured in different skeletal muscles and tissues. The profile of expression and the response to fasting and thyroid hormone of human UCP3 mRNA in transgenic mice with 16 kb of the human UCP3 gene were similar to that of the endogenous human gene. Various parts of the UCP3 promoter did not confer expression in transgenic lines. Inclusion of intron 1 resulted in an expression profile in skeletal muscle that was identical to that of human UCP3 mRNA. Further dissection of intron 1 revealed that distinct regions were involved in skeletal muscle expression, distribution among fibre types and response to fasting. The control of human UCP3 transcription in skeletal muscle is not solely conferred by the promoter, but depends on several cis-acting elements in intron 1, suggesting a complex interplay between the promoter and intronic sequences. [ABSTRACT FROM AUTHOR]

Uncoupling protein 3 (UCP3) is a mitochondrial transporter protein which, when over-expressed in mice, is associated with increased metabolic rate, increased feeding and low body weight. This phenotype probably reflects the increased levels of UCP3 partially uncoupling mitochondrial respiration from cellular ATP demands. Consistent with that, mitochondria isolated from muscles of mice that over-express UCP3 are less tightly coupled than those from wild-type mice but the degree of uncoupling is not modulated by likely physiological regulatory factors. To determine whether this also applies to intact muscle fibres, we tested the hypothesis that UCP3 constitutively (i.e. in an unregulated fashion) uncouples mitochondria in muscles from mice that over-expressed human UCP3 (OE mice). The rate of heat production of resting muscles was measured in vitro using bundles of fibres from soleus and extensor digitorum longus muscles of OE, wild-type (WT) and UCP3 knock-out mice. At 20°C, the only significant effect of genotype was that the rate of heat production of OE soleus (3.04 ± 0.16 mW g−1) was greater than for WT soleus (2.31 ± 0.05 mW g−1). At physiological temperature (35°C), the rate of heat production was independent of genotype and equal to the expected in vivo rate for skeletal muscles of WT mice. We conclude that at 35°C, the transgenic UCP3 was not constitutively active, but at 20°C in slow-twitch muscle, it was partially activated by unknown factors. The physiological factor(s) that activate mitochondrial uncoupling by UCP3 in vivo was either not present or inactive in resting isolated muscles. [ABSTRACT FROM AUTHOR]

Abstract: Uncoupling protein 3 (UCP3) is suggested to protect mitochondria against aging and lipid-induced damage, possibly via modulation of reactive oxygen species (ROS) production. Here we show that mice overexpressing UCP3 (UCP3Tg) have a blunted age-induced increase in ROS production, assessed by electron spin resonance spectroscopy, but only after addition of 4-hydroxynonenal (4-HNE). Mitochondrial function, assessed by respirometry, on glycolytic substrate was lower in UCP3Tg mice compared to wild types, whereas this tended to be higher on fatty acids. State 4o respiration was higher in UCP3Tg animals. To conclude, UCP3 overexpression leads to increased state 4o respiration and, in presence of 4-HNE, blunts the age-induced increase in ROS production. [Copyright &y& Elsevier]