Disease relevance of Ucp3

• The influence of sepsis, another condition characterized by muscle cachexia, on UCP3 expression and activity is not known [1].
• UCP3 is upregulated in various conditions characterized by skeletal muscle atrophy, including hyperthyroidism, fasting, denervation, diabetes, cancer, lipopolysaccharide (LPS), and treatment with glucocorticoids (GCs) [1].
• Our results point to the existence of sex-associated differences in the control of muscle UCP3 expression in response to overweight and fasting, with an impaired induction in female rats under both conditions [2].
• Concurrently, left ventricular UCP3 mRNA levels were significantly decreased with hypoxia (p<0.05) while UCP2 levels remained unchanged versus controls [3].
• The correlation of abdominal muscle UCP3 mRNA expression with overweight in males could be related to their relative resistance to gain weight after chronic overeating of a cafeteria diet, by the purported role of UCP3 in the regulation of lipid utilization [2].

Psychiatry related information on Ucp3

• By contrast, in the gastrocnemius muscle (a mixed fiber type muscle with a high capacity to shift between glucose and lipids as fuel substrate), mRNA expression of both UCP2 and UCP3 mRNA was found to be markedly up-regulated during food deprivation (when this tissue's thermogenesis is also decreased but its lipid fuel utilization is increased) [4].

High impact information on Ucp3

• UCP3 mRNA and protein levels increased 8.1-fold (+/- 1.1) and 2.8-fold (+/- 0.8), respectively, in the T(3)-treated vs. control rat gastrocnemius muscle [5].
• The recently cloned uncoupling protein homolog UCP3 is expressed primarily in muscle and therefore may play a significant role in the regulation of energy expenditure and body weight [5].
• These combined (31)P/(13)C NMR measurements were performed in control, 10-day triiodo-l-thyronine (T(3))-treated (model of increased UCP3 expression), and acute 2,4-dinitrophenol (DNP)-treated (protonophore and mitochondrial uncoupler) rats [5].
• Up-regulation of UCP2 and UCP3 gene expressions in skeletal muscle during food deprivation was found to persist at thermoneutrality (i.e., under conditions of reduced thermoregulatory thermogenesis) [4].
• The abilities of individual UCPs to prevent hyperglycemic PCD were assessed by adenovirus-mediated overexpression of UCP1 and UCP3 [6].

Chemical compound and disease context of Ucp3

• Therefore, amelioration of obesity by NO-1886 in OVX rats is possibly because of an the increased expression of fatty acid oxidation-related enzymes and UCP3, both of which are related to fatty acid transfer and fat use [7].
• The troglitazone-dependent decrease in UCP3 gene expression was accompanied by an increased weight gain in obese rats, while no such effect was observed in lean rats [8].

Biological context of Ucp3

• Leptin induced an upregulation of UCP3 mRNA in muscle, with no changes in BAT UCP1 mRNA [9].
• In contrast to BAT, UCP3 expression in skeletal muscle was increased in fasted rats and decreased during lactation [10].
• In rats fed high-fat diet the UCP-3 gene expression was augmented 2-fold in the skeletal muscle while UCP-2 mRNA levels were increased significantly (1.6-fold) in the epididymal WAT [11].
• The uncoupling protein homologs UCP2 and UCP3 have been proposed as candidate genes for the regulation of lipid metabolism [12].
• The present study examined the effect of chronic activation of 5'-AMP-activated protein kinase (AMPK) on the metabolic profile, including uncoupling protein-3 (UCP-3) and myosin heavy chain (MHC)-based fibre phenotype of rodent fast-twitch tibialis anterior muscle [13].

Anatomical context of Ucp3

• Expression of mitochondrial uncoupling protein 3 and adenine nucleotide translocase 1 genes in developing rat heart: putative involvement in control of mitochondrial membrane potential [14].
• In cultured myotubes, insulin increases the expression of glycolytic and lipogenic enzyme genes and inhibits the 9-cis retinoic acid-induced UCP3 expression [15].
• METHODS: Expression of UCP-3 mRNA in hindlimb muscles and plasma NEFA were measured after a single intraperitoneal injection of TZDs in healthy male rats [16].
• Our results are consistent with the interpretation that endurance exercise induces an adaptive increase in mitochondria that have a normal content of UCP3 [17].
• Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle [18].

Associations of Ucp3 with chemical compounds

• RA (7.5 mg/kg) increased UCP1 mRNA but decreased UCP2 and UCP3 mRNA by 50%, whereas methylprednisolone (65 mg/kg, two doses 24 h apart) suppressed all three uncoupling proteins by greater than 60% [19].
• Within the context of this hypothesis, we have compared, from fed and fasted rats, changes in gene expression of skeletal muscle UCP2 and UCP3 with those of carnitine palmitoyltransferase I and medium-chain acyl-CoA dehydrogenase, two key enzymes regulating lipid flux across the mitochondrial beta-oxidation pathway [12].
• Sterol regulatory element binding protein-1c expression and action in rat muscles: insulin-like effects on the control of glycolytic and lipogenic enzymes and UCP3 gene expression [15].
• RESULTS: Independent of which TZD was injected (50 micromol/kg), UCP-3 expression in gastrocnemius muscle was distinctly increased after 6 h (increase vs vehicle-injected control: pioglitazone, 10.3+/-3.2-fold, p=0.03; rosiglitazone, 8.7+/-1.2-fold, p=0.001; RWJ241947, 9.5+/-2.7-fold, p=0.03) [16].
• To elucidate the mechanism, here we compared the level of glucose transporter 4 (GLUT4) protein, uncoupling protein (UCP) 1 and UCP3 mRNA and protein expressions in the BAT under the same conditions [20].

Regulatory relationships of Ucp3

• Treatment of rats with the glucocorticoid receptor antagonist RU-38486 prevented the sepsis-induced increase in gene and protein expression of UCP3 [1].

Other interactions of Ucp3

• The reduction in mRNAs was reflected by a lowered UCP1 protein level, and to some extent, UCP3 protein [10].
• The present study provides evidence, for the first time, of the induction of UCP3 mRNA expression in skeletal muscle by leptin in nongenetically obese animals [9].
• The results support the view that mitochondrial energy conversion in heart changes during ontogeny and suggest the involvement of UCP3 and/or ANT1 in the control mechanism [14].
• Skeletal muscle heterogeneity in fasting-induced upregulation of genes encoding UCP2, UCP3, PPARgamma and key enzymes of lipid oxidation [12].
• Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling [3].

Analytical, diagnostic and therapeutic context of Ucp3

• UCP3 mRNA was 20% less in the denervated compared with the intact BAT, whereas UCP2 mRNA was unchanged with denervation [19].
• We examined UCP3 gene and protein expression in skeletal muscles from rats after cecal ligation and puncture and from sham-operated control rats [1].
• Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria [21].
• Quantification of FAT/CD36, GLUT4, UCP2 and UCP3 mRNAs was obtained by Northern blot analysis or RT-PCR [18].
• We examined the effects of 1-42 days of chronic low-frequency electrical stimulation (CLFS), applied to rat tibialis anterior (TA) for 10 h/day, on the expression of UCP-3 and concomitant changes in myosin heavy chain (MHC) protein expression and increases in oxidative capacity [22].

References