Search

The purpose of the experiment was to explore the response mechanism of preadipocytes after cold stress, and preliminarily identify the effect of oleic acid (OA) and myristic acid (MOA) in monounsaturated fatty acids on the expression of UCP1 and UCP3, and explore whether there was a relationship between monounsaturated fatty acids represented by OA and MOA and cold stress in cells. Oleic acid OA, myristic acid MOA, and Yanbian cattle preadipocytes were used as test materials. The preadipocytes were treated with OA and MOA for 96 h respectively, and the fat production in preadipocytes was determined by oil red staining and triglyceride content, and the relative surface amount of UCP1 and UCP3 was determined by qPCR. At the same time, the relative expression of UCP1 and UCP3 were measured after the adipocytes were treated with cold stress (4 ℃) for 0 h, 6 h, 12 h and 24 h before the treatment of untreated, OA and MOA for 96 h. The results showed that the expression levels of UCP1 and UCP3 were significantly decreased in OA group and MOA group (P<0.05); the expression of UCP1 increased significantly (P<0.05). The experiment found that the expression of UCP1 could be activated when the preadipocytes cultured for 96 h in 4 ℃ cold environment for 24 h, and the expression of UCP3 decreased with the time of cold stress treatment. The experiment preliminarily verify the inhibition of oleic acid and myristic acid on the two genes, providing basic data for the subsequent control of the application of molecular biological technology related to cold-resistant genes in animal husbandry. [ABSTRACT FROM AUTHOR]

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]

Background: Prescription of sports activity is an effective strategy for treating metabolic disorders, including obesity. The study aimed to determine the effect of 8 weeks of high-intensity interval training (HIIT) on PLIN5 and UCP3 gene expressions in skeletal muscle of obese rats.Methods: Fifty male Wistar rats were randomly divided into two groups of control receiving standard diet (CSD=20) and those with high-fat diet (HFD=30) for obesity induction (10 weeks). Ten rats from each group were selected to evaluate obesity (target weight: 350±20 g and serum triglyceride). The rest of high-fat diet group were randomly dividedinto 2 subgroups of obese control (OC=10) and HIIT high-fat diet (HIITHFD=10) and 10 in control standard diet rats were applied as the control standard diet in exercise phase. The HIIT protocol on the treadmill included 8 weeks, 5 sessions per week (10-degree incline) with 20 bouts (2 minutes maximum speed), and 1-minute active recovery. PLIN5 andUCP3 gene expressions in the gastrocnemius muscle were measured by real time-PCR and plasma triglycerides by ELISA.Results: The triglyceride (TG) level was higher in CSD compared to the HFD group. The weight, TG level and PLIN5, and UCP3 gene expressions significantly reduced in the experimental group compared to the CSD and OC groups.Conclusion: The values of energy intake, body weight, and PLIN5 and UCP3 gene expressions denoted to activated thermogenesis and fatty oxidation. Physical activity resulted in weight loss, and decreased gene expression to deal with this trend.

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]

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]

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.

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]

Abstract 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.

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]

Xu Jia,1,* Ziren Luo,2,* Ying Gao,3 Hua Liu,3 Xinghai Liu,3 Wenli Mai,3 Hong Liu,3 Qian Zheng3 1Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of China; 2School of Pharmacy, North Sichuan Medical College, Nanchong 637000, People’s Republic of China; 3Department of Physiology, North Sichuan Medical College, Nanchong 637007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian ZhengDepartment of Physiology, North Sichuan Medical College, Nanchong, 637007, People’s Republic of ChinaEmail 373969568@qq.comObjective: The protective effects of epigallocatechin gallate (EGCG) on interleukin-1β (IL-1β)-induced apoptosis were investigated in murine MIN6 pancreatic β-cells. The role of uncoupling protein-3 (UCP3) signaling in this process was also explored.Methods: After treatment with IL-1β and EGCG, cells were collected and analyzed. Cell viability was measured using the CCK8 assay and the function of β-cells was evaluated by analyzing insulin secretion. Detection of mitochondrial function in cells was performed by measuring mitochondrial membrane potential, the concentration of ATP and activity of ROS. Apoptosis was analyzed by Hochest33258 staining and flow cytometry. Expression levels of UCP3 were interrogated using immunohistochemistry, RT-PCR and Western blotting.Results: Compared with the control group, IL-1β treatment (20nM) for 24 h significantly decreased cell viability and insulin secretion, damaged mitochondrial function and increased ROS activity. Results also showed increased apoptosis and a decrease in UCP3 expression levels (p< 0.01). However, treatment with low (1mM) or high (5mM) concentrations of EGCG significantly decreased IL-1β-induced apoptosis (p< 0.01), restored mitochondrial function and subsequently increased UCP3 levels in IL-1β-induced β-cells (p< 0.01).Conclusion: These results suggest that EGCG protects against IL-1β-induced mitochondrial injury and apoptosis in β-cells through the up-regulation of UCP3.Keywords: EGCG, pancreatic β-cells, apoptosis, UCP3

Summary: Background: Sarcolipin and uncoupling protein 3 (UCP3) mediate muscle-based non-shivering thermogenesis (NST) to improve metabolic homeostasis. The impacts of maternal obesity (MO) and maternal exercise (ME) on NST in offspring muscle remain unexamined. Methods: Female mice were fed with a control diet or high fat diet to induce obesity. Then, obese mice were further separated into two groups: obesity only (OB) and OB plus daily exercise (OB/Ex). Fetal muscle was collected at embryonic day 18.5 and offspring mice at 3-month-old. Apelin administration during pregnancy and apelin receptor (APJ) knockout mouse were further used for investigating the mediatory role of APJ on muscle-based thermogenesis. To explore the direct effects of exercise on AMP-activated protein kinase (AMPK) downstream targets, AMPK knockout mouse was used. Findings: MO inhibited while ME activated AMPK and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in fetal muscle. AMPK activation increased sarcolipin expression, which inhibited the uptake of calcium ions into sarcoplasmic reticulum, thereby activating CaMKK2. Consistently, the expression of UCP3 and sarcolipin was suppressed due to MO but activated in ME fetal muscle. Importantly, changes of UCP3 and sarcolipin maintained in offspring muscle, showing the transgenerational effects. Furthermore, apelin administration during pregnancy mimicked the effects of ME on AMPK and CaMKK2 activation, and UCP3 and sarcolipin expression, underscoring the mediatory roles of apelin-AMPK signaling in improving fetal muscle development. Interpretation: ME, via activation of apelin signaling-AMPK axis, enhances NST gene expression in fetal and offspring muscle impaired due to MO, which intergenerationally protects offspring from diet-induced obesity and metabolic disorders. Funding: This work was supported by National Institutes of Health Grant R01-HD067449.

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.

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]

Objective: Abscisic acid (ABA) is a plant hormone also present and active in animals. In mammals, ABA regulates blood glucose levels by stimulating insulin-independent glucose uptake and metabolism in adipocytes and myocytes through its receptor LANCL2. The objective of this study was to investigate whether another member of the LANCL protein family, LANCL1, also behaves as an ABA receptor and, if so, which functional effects are mediated by LANCL1. Methods: ABA binding to human recombinant LANCL1 was explored by equilibrium-binding experiments with [3H]ABA, circular dichroism, and surface plasmon resonance. Rat L6 myoblasts overexpressing either LANCL1 or LANCL2, or silenced for the expression of both proteins, were used to investigate the basal and ABA-stimulated transport of a fluorescent glucose analog (NBDG) and the signaling pathway downstream of the LANCL proteins using Western blot and qPCR analysis. Finally, glucose tolerance and sensitivity to ABA were compared in LANCL2−/− and wild-type (WT) siblings. Results: Human recombinant LANCL1 binds ABA with a Kd between 1 and 10 μM, depending on the assay (i.e., in a concentration range that lies between the low and high-affinity ABA binding sites of LANCL2). In L6 myoblasts, LANCL1 and LANCL2 similarly, i) stimulate both basal and ABA-triggered NBDG uptake (4-fold), ii) activate the transcription and protein expression of the glucose transporters GLUT4 and GLUT1 (4-6-fold) and the signaling proteins AMPK/PGC-1α/Sirt1 (2-fold), iii) stimulate mitochondrial respiration (5-fold) and the expression of the skeletal muscle (SM) uncoupling proteins sarcolipin (3-fold) and UCP3 (12-fold). LANCL2−/− mice have a reduced glucose tolerance compared to WT. They spontaneously overexpress LANCL1 in the SM and respond to chronic ABA treatment (1 μg/kg body weight/day) with an improved glycemia response to glucose load and an increased SM transcription of GLUT4 and GLUT1 (20-fold) of the AMPK/PGC-1α/Sirt1 pathway and sarcolipin, UCP3, and NAMPT (4- to 6-fold). Conclusions: LANCL1 behaves as an ABA receptor with a somewhat lower affinity for ABA than LANCL2 but with overlapping effector functions: stimulating glucose uptake and the expression of muscle glucose transporters and mitochondrial uncoupling and respiration via the AMPK/PGC-1α/Sirt1 pathway. Receptor redundancy may have been advantageous in animal evolution, given the role of the ABA/LANCL system in the insulin-independent stimulation of cell glucose uptake and energy metabolism.

[Objective] The present study aimed to explore the association of single nucleotide polymorphism (SNP) and combined genotype of both uncoupling protein 3 (UCP3) and Forkhead box O 1 (FOXOl) with Zaosheng cattle growth traits. [Method] Via DNA seuqencing methods, the genotype polymorphisms within UCP3 and FOXOl genes in Zaosheng cattle populations were detected, and the associations of polymorphisms and combined genotypes with growth traits were analyzed. [ Result] Three SNPs ( g. 4439G >A, g. 4899G > A and g. SS7SG > A) were detected in within UCP3, and a mutant ( g. 92209C > T) in 3 ' -untranslated region of FOXOl were identified. Association analy- sis indicated that, both g. 4899G > A and g. 92209C > T remarkably influenced the body weight and chest circumference in Zaosheng cattle, and the GG and CC were excellent genotype, respectively. Moreover, the optical combined genotype of UCP3-FOXO1 was GG-GG-GG-CT, which was more effective on body weight and chest circumference than combined genotype of GG-GA-GA-CC (P < 0. 01 or P < 0. OS). [Conclusion] Both UCP3 and FOXOl directly or indirectly affected the growth traits of Zaosheng cattle, which could be used as candidate genes for breeding Zaosheng cattle with better growth traits. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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]

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.

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]

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]

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]

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.

Aim: Vitamin D 3 has been implicated in multiple reproductive events, whereas the effect of its bioactive metabolite 1α, 25 dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) on transcriptome profile of the placenta is unclear. The aim of this article is to determine transcriptome-wide profile caused by 1,25(OH) 2 D 3 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) 2 D 3 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) 2 D 3 were identified., Results: There were 180, 158, 161, and 174 differentially expressed genes after 0.1, 1, 10, and 100 nM 1,25(OH) 2 D 3 stimulation, respectively. KEGG pathway analysis displayed that "lipid and atherosclerosis" were significantly enriched at 0.1 and 1 nM 1,25(OH) 2 D 3 , 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) 2 D 3 . 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) 2 D 3 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., (© 2023 Japan Society of Obstetrics and Gynecology.)

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]