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PubMed2002

Uncoupling protein 2 in primary pain and temperature afferents of the spinal cord.

Uncoupling protein 2 (UCP2) is a mitochondrial protonophore that regulates cellular energy homeostasis. In this study, we explored the expression of UCP2 in the spinal cord. UCP2 was expressed in the substantia gelatinosa and ventral horn of the rodent and primate spinal cord. In all of these areas, UCP2 expression was associated with axons and axon terminals and direct appositions between UCP2-immunoreactive fibers and NMDA glutamate receptors-containing perikarya were frequently detected. All of the UCP2-labeled processes were also immunoreactive for substance P. The expression of UCP2 in primary sensory afferents of the spinal cord suggests that this mitochondrial uncoupler is involved in the mechanism of pain and temperature sensation.

Afferent Pathways↗

PubMedDate not supplied

Molecular identification of uncoupling proteins 2 and 3 in a carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii).

This study investigated the expression of uncoupling proteins 2 and 3 (UCP2 and UCP3) in the carnivorous marsupial Sarcophilus harrisii. The current study used molecular techniques to ascertain whether this species expresses UCP2 and/or UCP3. This species increases nonshivering thermogenesis in response to cold exposure and norepinephrine, although our previous study was unable to demonstrate the presence of brown adipose tissue or uncoupling protein 1. Samples of skeletal muscle and white adipose tissues were taken from five S. harrisii pre- and post-cold acclimation (2 degrees -3 degrees C for 2 wk). The tissues were examined for UCP2 and UCP3 expression through Western blots and reverse transcriptase polymerase chain reaction, with subsequent sequencing to ensure identification of the desired gene. These data suggest that S. harrisii expresses UCP2 but not UCP3. The sequencing of the amplified S. harrisii UCP2 cDNA has revealed a 76% homology with human UCP2 cDNA and a 72% homology with rat UCP2 cDNA. The expression of UCP2 but not UCP3 suggests that UCP2 is conserved from a common ancestor to both the Marsupialia and the Eutheria taxa.

Acclimatization↗

PubMed1998

Molecular screening of uncoupling protein 2 gene in patients with noninsulin-dependent diabetes mellitus or obesity.

Uncoupling protein 2 (UCP2), a member of the family of mitochondrial carrier proteins, has been implicated in the control of whole-body energy balance. The coding region of the human UCP2 gene has now been shown to comprise six exons, and the sequences of the exon-intron boundaries were determined. With the use of this sequence information, 25 Japanese patients with obesity and noninsulin-dependent diabetes mellitus (NIDDM) and 25 subjects with simple obesity were screened for mutations in the entire coding region of UCP2 by PCR and single-strand conformation polymorphism analysis. Two nucleotide polymorphisms resulting in Ala55 --> Val and Ala232 --> Thr substitutions were detected. With the use of PCR and restriction fragment length polymorphism analysis, the allele frequencies for each of these polymorphisms were determined in 210 Japanese patients with NIDDM, 42 obese individuals, and 218 normal control subjects. The frequency of the Val55 allele did not differ significantly among the NIDDM group (46.0%), the obesity group (48.8%), and the normal control group (48.4%). The Thr232 allele was detected in only three subjects, who were heterozygotes and in the NIDDM group (allele frequency, 0.7%). However, expression in yeast of the human wild-type UCP2 protein and UCP2 containing Thr232 revealed no difference in functional activity. These results indicate that the Ala55 --> Val and Ala232 --> Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.

Adult↗

PubMed2000

Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation.

Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and partially uncouples respiration from ATP synthesis when expressed in recombinant yeast mitochondria. We generated a highly sensitive polyclonal antibody against human UCP2. Its reactivity toward mitochondrial proteins was compared between wild type and ucp2(-/-) mice, leading to non-ambiguous identification of UCP2. We detected UCP2 in spleen, lung, stomach, and white adipose tissue. No UCP2 was detected in heart, skeletal muscle, liver, and brown adipose tissue. The level of UCP2 in spleen mitochondria is less than 1% of the level of UCP1 in brown adipose tissue mitochondria. Starvation and LPS treatments increase UCP2 level up to 12 times in lung and stomach, which supports the hypothesis that UCP2 responds to oxidative stress situations. Stimulation of the UCP2 expression occurs without any change in UCP2 mRNA levels. This is explained by translational regulation of the UCP2 mRNA. We have shown that an upstream open reading frame located in exon two of the ucp2 gene strongly inhibits the expression of the protein. This further level of regulation of the ucp2 gene provides a mechanism by which expression can be strongly and rapidly induced under stress conditions.

Animals↗

PubMed2006

Uncoupling protein 2 promoter polymorphism -866G/A, central adiposity, and metabolic syndrome in Asians.

A polymorphism in the promoter region of uncoupling protein 2 gene -866G/A has been associated with its expression levels in adipose tissue, the risk of obesity, and metabolic abnormalities. Our purpose was to examine the associations of -866G/A with body fat and the risk of metabolic syndrome in a random sample of 4018 Asians (1858 men and 2160 women) from three ethnic groups (Chinese, Malay, and Indian). The minor allele frequency of -866G/A polymorphism in South Asians was similar to that in whites. After adjustment for covariates including age, cigarette smoking, and physical activity, the -866A/A genotype was associated with higher waist-to-hip ratio as compared with the wild-type genotype in Chinese and Indian men (p = 0.018 and p = 0.046, respectively). Moreover, Indian men with -866A/A genotype had a significantly increased risk of metabolic syndrome as compared with those homozygous for the wild-type (odds ratio, 2.66; 95% confidence interval, 1.21 to 5.88; p = 0.015). Such a risk was mainly caused by the excess presence of hypertriglyceridemia and central obesity. Our findings indicate that the uncoupling protein 2 gene -866G/A polymorphism may increase the risks of central obesity and metabolic syndrome, with greater effects on Asian men.

Adiposity↗

PubMed1999

Uncoupling protein 2 from carp and zebrafish, ectothermic vertebrates.

Uncoupling protein 1 (UCP1) is of demonstrated importance in mammalian thermogenesis, and early hypotheses regarding the functions of the newly discovered UCP homologues, UCP2, UCP3 and others, have focused largely on their potential roles in thermogenesis. Here we report the amino acid sequences of two new UCPs from ectothermic vertebrates. UCPs from two fish species, the zebrafish (Danio rerio) and carp (Cyprinus carpio), were identified in expressed sequence tag databases at the European Molecular Biology Laboratory. cDNAs from a C. carpio 'peritoneal exudate cell' cDNA library and from a D. rerio 'day 0 fin regeneration' cDNA library were obtained and fully sequenced. Each cDNA encodes a 310 amino acid protein with an average 82% sequence identity to mammalian UCP2s. The fish UCP2s are about 70% identical to mammalian UCP3s, and 60% identical to mammalian UCP1s. Carp and zebrafish are ectotherms--they do not raise their body temperatures above ambient by producing excess heat. The presence of UCP2 in these fish thus suggests the protein may have function(s) not related to thermogenesis.

Amino Acid Sequence↗

PubMed2002

Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet.

Uncoupling protein 2 (UCP2) may act as an important regulator of insulin secretion. In this study, beta-cell function in UCP2-deficient mice was examined after a 45% high-fat diet (HFD) to assess its role during the development of diet-induced type 2 diabetes. HFD-fed UCP2 (-/-) mice have lower fasting blood glucose and elevated insulin levels when compared with wild-type (WT) mice. UCP2 (-/-) mice also have enhanced beta-cell glucose sensitivity compared with WT mice after HFD, a result that is due in part to the deterioration of glucose responsiveness in WT mice. HFD-fed UCP2 (-/-) mice have increased insulin secretory capacity as a result of increased pancreatic beta-cell mass and insulin content per islet. Islets from WT mice exposed to 0.5 mmol/l palmitate for 48 h have significantly reduced mitochondrial membrane potential, ATP concentrations, and glucose responsiveness compared with UCP2 (-/-) islets, suggesting that elevated UCP2 in WT mice increases proton leak and decreases mitochondrial ATP production. Highly increased carnitine palmitoyl transferase-1 gene expression in UCP2 (-/-) mice is suggestive of enhanced fatty acid oxidizing capacity, particularly after HFD stress. These results further establish UCP2 as a component in glucose sensing and suggest a possible new aspect of UCP2 function during the progression of type 2 diabetes.

Animals↗

PubMed2004

Role of uncoupling protein 2 (UCP2) expression and 1alpha, 25-dihydroxyvitamin D3 in modulating adipocyte apoptosis.

We previously found that 1alpha, 25-dihydroxyvitamin D3 [1alpha, 25-(OH)2-D3] modulates adipocyte lipid metabolism via a Ca2+-dependent mechanism and inhibits adipocyte UCP2 expression, indicating that the anti-obesity effects of dietary calcium are mediated by suppression of 1alpha, 25-(OH)2-D3 levels. However, because UCP2 reduces mitochondrial potential, we have evaluated the roles of UCP2, mitochondrial uncoupling, and 1alpha, 25-(OH)2-D3 in adipocyte apoptosis. Overexpressing UCP2 in 3T3-L1 cells induced marked reductions in mitochondrial potential (Deltapsi) and ATP production (P<0.01), increases in the expression of caspases (P<0.05), and a decrease in Bcl-2/Bax expression ratio (P<0.01). Physiological doses of 1alpha, 25-(OH)2-D3 (0.1-10 nM) restored mitochondrial Deltapsi in LI-UCP2 cells and protected against UCP2 overexpression-induced apoptosis (P<0.01), whereas a high dose (100 nM) stimulated apoptosis in 3T3-L1 and L1-UCP2 cells (P<0.05). 1alpha, 25-(OH)2-D3 stimulated cytosolic Ca2+ dose-dependently in both 3T3-L1 and L1-UCP2 cells. However, physiological doses suppressed mitochondrial Ca2+ levels by approximately 50% whereas the high dose increased mitochondrial Ca2+ by 25% (P<0.05); this explains stimulation of apoptosis by the high dose of 1alpha, 25-(OH)2-D3. Using high-calcium diets to suppress 1alpha, 25-(OH)2-D3 stimulated adipose tissue apoptosis in aP2 transgenic mice (P<0.01), suggesting that increasing dietary calcium stimulates adipose apoptosis and thereby further contributes to an anti-obesity effect of dietary calcium.

3T3-L1 Cells↗

PubMed1998

Rat uncoupling protein 2 (UCP2): expression in obese ventromedial hypothalamus (VMH)-lesioned animals.

BACKGROUND: The family of uncoupling proteins is thought to play an important role in the regulation of energy metabolism by uncoupling the respiratory chain reactions from ATP synthesis. The recently discovered uncoupling protein 2 (UCP2) is upregulated in genetically obese rodent models and during long term high fat feeding. AIM: We have examined the UCP2 mRNA levels in liver, heart and white adipose tissue (WAT) of obese ventromedial hypothalamus (VMH)-lesioned rats, during the dynamic and the early stage of the static phase of obesity, before the appearance of most of the metabolic perturbations associated with long term established obesity. RESULTS: The amount of UCP2 mRNA was not increased in any tissue of VMH-lesioned rats relative to control animals during the dynamic phase nor during the early static phase of obesity. CONCLUSION: These results indicate that in the rat, obesity does not necessarily lead to an increase in UCP2 expression and suggest that the up-regulation of UCP2 described in other models may be secondary to metabolic perturbations, rather than to a direct adaptative response to the increased adipose tissue content of the organism.

Animals↗

PubMed2005

mRNA for pancreatic uncoupling protein 2 increases in two models of acute experimental pancreatitis in rats and mice.

Uncoupling-protein 2 (UCP2) is a mitochondrial protein that appears to be involved in cellular oxidant defense and in the regulation of oncotic cell death, both of which are important features of acute pancreatitis. However, UCP2 expression in acute pancreatitis has not been previously reported. In the current experiments, pancreatic gene expression was studied by real-time reverse-transcription/polymerase chain reaction and Northern blots. Two models of acute experimental pancreatitis were investigated: cerulein-induced pancreatitis in mice at two different time points and taurocholate-induced pancreatitis in rats at two degrees of severity. After cerulein administration, acinar injury and leukocyte infiltration was significantly higher at 24 h compared with 12 h after the first injection of cerulein (P<0.05, P<0.005, respectively). UCP2 mRNA was unchanged at 12 h but was nearly 12-fold greater than control levels after 24 h (P<0.001). UCP2 gene expression correlated with acinar injury (r=0.69; P<0.001). By 72 h after taurocholate administration, the severe group had more necrosis than the mild group (P<0.005). Pancreatic UCP2 mRNA was increased fourfold in the severe group compared with controls (P<0.01). UCP2 expression correlated with parenchymal necrosis (r=0.61; P<0.01). Thus, pancreatic UCP2 mRNA increased in two models of acute pancreatitis. The increase in UCP2 gene expression was correlated with the severity of the disease. Up-regulation of UCP2 in the pancreas may be a protective response to oxidative stress, but this increase may also have a negative influence on cellular energy metabolism. Therefore, acinar UCP2 may be an important modifier of the severity of acute pancreatitis.

Acute Disease↗

PubMed2004

A common polymorphism of uncoupling protein 2 gene is associated with hypertension.

OBJECTIVES: The genes responsible for obesity are also candidate genes for obesity-related conditions, such as hypertension and type 2 diabetes. A functional polymorphism in the uncoupling protein 2 (UCP2) promoter has been reported to be associated with obesity in Caucasians. To clarify the contribution of this polymorphism to obesity and related conditions, we studied the association of the -866 G/A polymorphism of the UCP2 gene with obesity, hypertension and type 2 diabetes mellitus. METHODS: A total of 632 unrelated Japanese subjects were studied: 342 type 2 diabetic patients (among them, 158 patients complicated with hypertension), 156 hypertensive patients without diabetes mellitus and 134 control subjects. The -866 G/A polymorphism of UCP2 was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: The frequency of the minor A allele was significantly higher in Japanese than in Caucasians (48.9 versus 37.2%, P=0.01). In contrast to the significant association with obesity in Caucasians, the polymorphism was not associated with obesity in Japanese. The polymorphism, however, was significantly associated with hypertension in Japanese (frequency of A allele: 51.8% in hypertensives versus 46.6% in normotensives, P<0.05). No significant difference was observed in body mass index (BMI), fasting insulin level or HOMA-R between patients with different genotypes. CONCLUSION: These data indicate that the polymorphism of the UCP2 gene is associated with hypertension, and suggest the possibility of UCP2 as a target molecule for studies on the etiology and treatment of hypertension.

Adult↗

PubMed2004

[Expression of uncoupling protein 2 in periimplantation endometrium and its relationship with infertility].

OBJECTIVE: To study the expression of uncoupling protein 2 (UCP2) mRNA and protein in the endometrium and its changes during periimplantation period in relation to infertility. METHODS: In situ hybridation and Western blotting were used to detect 21 endometrium specimens from normal cycling women during different menstrual phases, 22 secretory endometrium specimens from infertile women and 7 decidual and chorionic villus specimens. RESULTS: UCP2 mRNA and protein were detected in the endometrium and decidua besides, the trophoblast, and UCP2 level in the endometrium increased during pregnancy. Compared with normal women, women with hydrosalpinges had significantly stronger endometrial UCP2 expression in the mid-luteal stage. CONCLUSIONS: UCP2 down-regulates reactive oxygen species and plays a role in the regulation of inflammatory events to prepare for embryo implantation. Strong endometrial UCP2 expression might be an important reason that hydrosalpinges affect embryo implantation.

Adult↗

PubMed2004

Cardiovascular risk in healthy men and markers of oxidative stress in diabetic men are associated with common variation in the gene for uncoupling protein 2.

BACKGROUND: Oxidative stress reduces total antioxidant status (TAOS) and is implicated in atherogenesis. Mitochondrial uncoupling protein 2 (UCP2) negatively regulates reactive oxygen species generation. The UCP2 gene demonstrates a common functional promoter variant (-866G>A). METHODS AND RESULTS: Amongst 465 diabetic men (age 61.7 +/- 13.3 years), an association of the UCP2-866A allele with significantly lower TAOS in those without CHD was even more pronounced in those with CHD (TAOS 30.1 +/- 16.1% vs. 41.6 +/- 12.4% for AA vs. GG; P=0.016). In a sample of 20 diabetic men selected for homozygosity for the UCP2-866G>A variant, matched for baseline characteristics, plasma markers of oxidative stress in those with CHD were significantly higher in AA genotype men (TAOS 31.7 +/- 7.3% vs. 52.6 +/- 6.3%; P=0.001 and F2-isoprostanes 220.6 +/- 37.2 pg ml(-1) vs. 109.9 +/- 51.1 pg ml(-1); P=0.005 for AA vs. GG). Amongst 2695 healthy men (age 56.1 +/- 3.5 years) prospectively studied for a median 10.2 years, AA homozygotes had a highly significant doubling in CHD risk after adjustment for established risk factors (HR 1.99 [1.37-2.90]; P=0.002). Risk associated with this genotype was substantially increased by the presence of other risk factors (obesity, hypertension and diabetes). CONCLUSIONS: This study provides the first in vivo evidence of a role for UCP2 in modifying oxidative stress and CHD risk in humans.

Antioxidants↗

PubMed2004

Overexpression of uncoupling protein 2 in THP1 monocytes inhibits beta2 integrin-mediated firm adhesion and transendothelial migration.

OBJECTIVE: Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates production of reactive oxygen species in macrophages. Previous studies have shown that selective genetic disruption of UCP2 in bone marrow cells results in excess accumulation of monocytes/macrophages in the vascular wall of hypercholesterolemic low-density lipoprotein receptor-deficient (LDLR-/-) mice. Here we investigated whether UCP2 regulates expression of genes involved in monocyte recruitment. METHODS AND RESULTS: UCP2 overexpression in THP1 monocytes, which induced a 10-fold increase in mitochondrial UCP2 protein levels, reduced steady-state level of intracellular reactive oxygen species (ROS) and H2O2-induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H2O2-triggered intracellular calcium mobilization, and less protein and mRNA levels of beta2 integrins, most notably CD11b. UCP2 overexpression reduced beta2 integrin-mediated firm adhesion of monocytes to either tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic endothelial cell (HAEC) monolayers or to plates coated with intercellular adhesion molecule-1, not vascular cell adhesion molecule-1. UCP2 overexpression also inhibited cell spreading and actin polymerization in monocytes treated with TNF-alpha and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1-induced transmigration of monocytes through HAEC monolayers. CONCLUSIONS: Mitochondrial UCP2 in circulating monocytes may prevent excessive accumulation of monocytes/macrophages in the arterial wall, thereby reducing atherosclerotic plaque formation.

Actins↗

PubMed2004

Second transmembrane domain of human uncoupling protein 2 is essential for its anion channel formation.

Uncoupling proteins (UCP) are known to transport anions, such as Cl-, in addition to H+ transport. Although H+ transport by UCP is clearly involved in thermogenesis, the mechanism of its anion transport is not clearly understood. In this study, we examined the anion channel characteristics of the six individual helical transmembrane (TM) domains of the human UCP2. The second TM domain peptide (TM2) forms multi-state channels by assemblies of conductive oligomers. Furthermore, the TM2 exhibited voltage-dependent anion channels with properties comparable to those of UCP1 chloride channel. However, the other five TM peptides did not form UCP1-like channels. Moreover, an analog of TM2 in which two Arg residues were substituted by Ala residues did not form stable channels, implying the significance of Arg residues for anion transport. These results suggest that the anion channel structure of UCP2 protein is oligomeric and the second TM domain is essential for the voltage-dependence of this anion channel.

Amino Acid Sequence↗

PubMed2006

Changes in fat mass after initiation of maintenance dialysis is influenced by the uncoupling protein 2 exon 8 insertion/deletion polymorphism.

BACKGROUND: A high body mass index (BMI) has been reported to confer a survival advantage in end-stage renal disease (ESRD) patients. On the other hand, body fat accumulation, especially visceral adipose tissue, is an important risk factor for cardiovascular disease, as well as a clinically important source of adipokines. Uncoupling protein 2 (UCP2) uncouples respiration from ATP synthesis, thus regulating energy expenditure and fat oxidation. In this longitudinal cohort study, we investigated the impact of the UCP2 insertion/deletion (ins/del) polymorphism on body composition changes in ESRD patients starting dialysis. METHODS: A total of 222 incident Caucasian ESRD patients (mean age 53 +/- 12 years; 60% males) were investigated close to the start of dialysis with peritoneal dialysis (PD; n = 126) or haemodialysis (HD; n = 96), and again after about 1 year (n = 159). Genotyping of the UCP2 ins/del polymorphism was performed in the patients and in 207 healthy controls. Dual-energy X-ray absorptiometry was conducted at baseline and after 1 year to monitor body composition. RESULTS: While HD patients and PD patients with the ins/del genotype did not display any changes in body composition, the 48 PD patients with the del/del genotype that completed follow-up had a significant increase; DeltaBMI (0.7 +/- 1.8 kg/m(2)), Deltabody fat mass (3.5 +/- 3.8 kg) and Deltatruncal fat mass (1.7 +/- 1.2 kg). In a multiple linear regression analysis, the del/del genotype was an independent predictor of the increase in truncal fat mass in PD patients (F-ratio = 7.99, P < 0.05) together with age and diabetes mellitus. CONCLUSIONS: PD patients, but not HD patients, with the UCP2 del/del genotype showed a significant increase in total and truncal fat mass during the first year of dialysis therapy, suggesting a possible role for UCP2 in dissipating the excess energy of a high-glucose environment.

Adipose Tissue↗

PubMed2002

Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages.

The expression of uncoupling protein 2 (UCP2) was reduced in macrophages after stimulation with lipopolysaccharide (LPS). The physiological consequence and the regulatory mechanisms of the UCP2 down-regulation by LPS were investigated in a macrophage cell line, RAW264 cells. UCP2 overexpression in RAW264 cells transfected with eukaryotic expression vector containing ucp2 cDNA markedly reduced the production of intracellular reactive oxygen species. Furthermore, in the UCP2 transfectant, nitric oxide (NO) synthesis, inducible NO synthase (NOS II) protein, NOS II mRNA, and NOS II promoter activity were definitely decreased after LPS stimulation compared with those in parental RAW264 or RAW264 cells transfected with the vector alone. Reporter assays suggested that an enhancer element was located in the region of intron 2 of the UCP2 gene and that the UCP2 expression was down-regulated not by the 7.3-kb promoter region but by the 5' region of the UCP2 gene containing two introns. Deletion of intron 2 resulted in the low transcriptional activities and abolishment of the LPS-associated negative regulation. In addition, the mRNA expression of transfected UCP2 was suppressed in RAW264 cells transfected with expression vector containing UCP2 genomic DNA, but was markedly increased in cells transfected with the vector containing UCP2 intronless cDNA. These findings suggest that the LPS-stimulated signals suppress UCP2 expression by interrupting the function of intronic enhancer, leading to an up-regulation of intracellular reactive oxygen species, which activate the signal transduction cascade of NOS II expression, probably to ensure rapid and sufficient cellular responses to a microbial attack.

Animals↗

PubMed2001

Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice.

Thermogenic activity in brown adipose tissue (BAT) decreases during lactation; the down-regulation of the gene encoding uncoupling protein 1 (UCP1) is involved in this process. Our studies show that UCP2 mRNA expression does not change during the breeding cycle in mice. In contrast, UCP3 mRNA is down-regulated in lactation but it recovers after weaning, in parallel with UCP1 mRNA. This leads to a decrease in the content of UCP3 in BAT mitochondria during lactation. Lowering the energy-sparing necessities of lactating dams by decreasing litter size or feeding with a high-fat diet prevented the down-regulation of UCP1 mRNA and UCP3 mRNA. In most cases this resulted in a less marked decrease in UCP1 and UCP3 protein in BAT mitochondria owing to lactation. Fasting for 24 h caused a different response in UCP1 and UCP3 mRNA expression: it decreased UCP1 mRNA levels but had no effect on UCP3 mRNA abundance in virgin mice; it even increased UCP3 mRNA expression in lactating dams. These changes did not lead to modifications in UCP1 or UCP3 protein abundance. Whereas acute treatment with peroxisome-proliferator-activated receptor (PPAR)alpha and PPARgamma agonists increased UCP1 mRNA levels only in lactating dams, UCP3 mRNA expression was induced by both kinds of PPAR activator in lactating dams and by PPARalpha agonists in virgin mice. It is concluded that modifications of UCP2 mRNA levels are not part of the physiological adaptations taking place in BAT during lactation. In contrast, the down-regulation of UCP3 mRNA expression and mitochondrial UCP3 content is consistent with a role for the gene encoding UCP3 in the decrease in metabolic fuel oxidation and thermogenesis in BAT during lactation.

Adipose Tissue, Brown↗