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Results for “Uncoupling Protein 1”

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PubMed2001

GG-genotype in the promotor region of uncoupling-protein-1 gene is associated with lower level of dehydroepiandrosterone in type 2 diabetes.

The A-->G (-3826) point mutation within the distal region of the uncoupling-protein-1 (UCP-1) promoter is possibly involved in the development of obesity, diabetes and related disorders. DHEAS has been found to stimulate expression of UCP-1-mRNA. The aim of our study was to evaluate the prevalence of the three UCP-1 genotypes in type 2 diabetic patients out of a population based sample. Possible associations of A-->G mutation with serum levels of DHEAS and with obesity, diabetes and retinopathy were examined. - In 549 diabetic patients (312 males and 237 females) out of a population-based sample UCP-1 genotype was determined by genomic PCR and Bcl-I-RFLP analysis. Serum levels of DHEAS were measured by ELISA. - Genotype frequencies were: GG genotype, 4.4% (n= 24); AG genotype 37.3% (n=205) and AA genotype 58.3% (n= 320). The genotype groups were comparable with respect to sex, BMI, HbA1c, systolic blood pressure (BP), retinopathy and also to serum levels of C-peptide, leptin and cortisol. Serum levels of DHEAS were lowest in GG-genotype as compared to AG and AA (GG: 1.8+/-1.5 micromol/l, AG: 2.2+/-1.8 micromol/l, AA: 2.6+/-2.1 micromol/l; AA vs AG, AA vs GG: p<0.05). In a multiple linear regression analysis, which controlled for age, C-peptide, cholesterol, systolic BP, BMI, and HbA1c DHEAS was significantly negatively correlated with levels of cholesterol and positively with systolic BP only in females (p<0.05). - Allelic frequency for G in diabetic subjects was 0.23 which was similar as compared to a non-diabetic population examined by us in an earlier study. GG-genotype was associated with low levels of DHEAS in diabetic patients but not with retinopathy. We suggest a role for UCP-1 polymorphism in the pathogenesis of obesity and arteriosclerosis. This hypothesis, however, needs further investigation.

Aged↗

PubMed2006

Feeding scallop shell powder induces the expression of uncoupling protein 1 (UCP1) in white adipose tissue of rats.

Previously we found that the organic components in scallop shell promote lipolysis in differentiated 3T3-L1 and C3H10T1/2 adipocyte cells, and that incorporating scallop shell powder into the diet of rats reduced the amount of white adipose tissue. In this study, we used RT-PCR to investigate the effect of ingesting scallop shell powder on the gene expression profile of uncoupling proteins (UCPs) regulating energy metabolism in rats. Feeding of scallop shell powder increased mRNA levels of UCP1 and UCP2 in white adipose tissue. By contrast, scallop shell powder had no effect on the expression of UCP1 in brown adipose tissue, although the expression level of UCP2 mRNA decreased significantly. These results suggest that feeding scallop shell powder increases gene expression of UCP1 that may regulate energy metabolism in white adipose tissue, resulting in the observed reduction in weight of white adipose tissue.

Adipose Tissue, White↗

PubMed2004

p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene.

It is well established that catecholamine-stimulated thermogenesis in brown fat requires beta-adrenergic elevations in cyclic AMP (cAMP) to increase expression of the uncoupling protein 1 (UCP1) gene. However, little is known about the downstream components of the signaling cascade or the relevant transcription factor targets thereof. Here we demonstrate that cAMP- and protein kinase A-dependent activation of p38 mitogen-activated protein kinase (MAPK) in brown adipocytes is an indispensable step in the transcription of the UCP1 gene in mice. By phosphorylating activating transcription factor 2 (ATF-2) and peroxisome proliferator-activated receptor gamma (PPARgamma) coativator 1alpha (PGC-1alpha), members of two distinct nuclear factor families, p38 MAPK controls the expression of the UCP1 gene through their respective interactions with a cAMP response element and a PPAR response element that both reside within a critical enhancer motif of the UCP1 gene. Activation of ATF-2 by p38 MAPK additionally serves as the cAMP sensor that increases expression of the PGC-1alpha gene itself in brown adipose tissue. In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis.

Adipocytes↗

PubMed2005

Identification of a functioning mitochondrial uncoupling protein 1 in thymus.

We present evidence that rat and mouse thymi contain mitochondrial uncoupling protein (UCP 1). Reverse transcriptase-PCR detected RNA transcripts for UCP 1 in whole thymus and in thymocytes. Furthermore, using antibodies to UCP 1 the protein was also detected in mitochondria isolated from whole thymus and thymocytes but not in thymus mitochondria from UCP 1 knock-out mice. Evidence for functional UCP 1 in thymus mitochondria was obtained by a comparative analysis with the kinetics of GDP binding in mitochondria from brown adipose tissue. Both tissues showed equivalent B(max) and K(D) values. In addition, a large component of the nonphosphorylating oxygen consumption by thymus mitochondria was inhibited by GDP and subsequently stimulated by addition of nanomolar concentrations of palmitate. UCP 1 was purified from thymus mitochondria by hydroxyapatite chromatography. The isolated protein was identified by peptide mass mapping and tandem mass spectrometry by using MALDI-TOF and LC-MS/MS, respectively. We conclude that the thymus contains a functioning UCP 1 that has the capacity to regulate metabolic flux and production of reactive oxygen-containing molecules in the thymus.

Amino Acid Sequence↗

PubMed2001

Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.

Adult↗

PubMed2003

Developmental changes in uncoupling protein 1 and F1-ATPase subunit levels in the golden hamster brown adipose tissue mitochondria as determined by electron microscopy in situ immunocytochemistry.

The postnatal developmental changes in mitochondrial uncoupling protein 1 (UCP 1) and F1-ATP synthase (ATPase) subunit levels in the interscapular brown adipose tissue (BAT) were studied in golden Syrian hamsters (Mesocricetus auratus) using electron microscopy in situ immunocytochemistry. The relatively low initial density of 5 nm gold conjugated anti-UCP 1 immunocomplexes gradually increased from 7- to 21-day-old animals and numerous immunocomplexes were found on the mitochondrial membranes of adult hamsters. At the age of 7-9 days, a positive reaction was also detected in the cytoplasm of BAT adipocytes. Immunolocalization of F1-ATPase subunit indicated its presence in BAT mitochondria and cytoplasm of 7- to 9-day-old animals. However, contrary to UCP 1, intensity of the immunostaining of F1-ATPase subunit rapidly decreased both in mitochondria and cytoplasm between the 10th and 21st postnatal day and it became stabilized in adult animals at a very low level restricted to mitochondria. These results confirm that profound changes in the enzymatic apparatus of BAT mitochondrial membranes, leading to formation of thermogenic mitochondria, occur not until the early postnatal period of hamster ontogenetic development.

Adipose Tissue, Brown↗

PubMed2003

Effects of uncoupling protein 1 and beta3-adrenergic receptor gene polymorphisms on body size and serum lipid concentrations in Japanese women.

OBJECTIVES: To investigate whether the -3826 A-G point mutation of the uncoupling protein 1 (UCP1) gene and the Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) gene are associated with increased susceptibility to weight gain and hyperlipidemia in postmenopausal women. METHODS: We genotyped 312 Japanese women for UCP1 and beta3-AR gene polymorphisms, and investigated their effects on anthropometrical parameters, serum lipid concentrations, and their changes after 4 years. RESULTS: Although body mass index (BMI), serum triglyceride, total cholesterol, and low-density lipoprotein levels were significantly higher and high-density lipoprotein levels significantly lower in postmenopausal (n=182) than in premenopausal (n=99) women, there was no significant difference in these parameters between carriers and non-carriers of the G allele in the postmenopausal women. In the premenopausal women, BMI and the 4-year change in body weight (BW) of carriers of the G allele were significantly higher than those of non-carriers of the G allele (P=0.022 and 0.048, respectively). In the postmenopausal women, the 4-year change in the level of serum triglyceride of carriers of the G allele was significantly higher (P=0.049), and the change of high-density lipoprotein was significantly lower (P=0.020) than those of non-carriers of the G allele. The beta3-AR polymorphism showed no apparent affect on these parameters. CONCLUSIONS: The -3826 A-G polymorphism of the UCP1 gene is associated with an increase in BW of premenopausal women and with the 4-year changes in serum triglyceride and high-density lipoprotein levels in postmenopausal women.

Adult↗

PubMed2004

The Arg64 allele of the beta 3-adrenoceptor gene but not the -3826G allele of the uncoupling protein 1 gene is associated with increased leptin levels in the Spanish population.

To determine whether there are variations in leptin levels according to the beta(3)-adrenoceptor (beta(3)-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826A-->G polymorphisms, given the regulatory role of catecholamines through the beta(3)-AR in leptin production and the previously reported association of the UCP1 -3826A-->G variant with obesity. A total of 160 men and 172 women randomly chosen from a nationwide population-based obesity cross-sectional survey in Spain were studied. Body mass index (BMI), waist-to-hip ratio (WHR), leptin, insulin, fasting and 2-hour post-glucose load glycemia, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-, and total cholesterol, and triglyceride plasma levels were measured. beta(3)-AR Trp64Arg and UCP1 -3826A-->G genotypes were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). UCP1 -3826G allele frequency was higher in men than in women (0.31 v 0.22, P = .015) and in obese women than in non-obese women (0.31 v 0.17, P = .008). Women carriers of the Arg64 or the alleles also showed higher leptin levels than noncarriers. Multiple linear regression analysis showed that the Arg64 allele is associated with higher leptin levels after the adjustment for gender, age, WHR, and the degree of glucose tolerance. In conclusion, the beta(3)-AR Trp64Arg polymorphism might have an impact on the mechanisms involved in leptin release from adipose tissue. Furthermore, our results agree with the previously reported association between UCP1 -3826G allele and obesity and point to a gender-related effect.

Adipocytes↗

PubMed1998

DNA polymorphism in the uncoupling protein 1 (UCP1) gene has no effect on obesity related phenotypes in the Swedish Obese Subjects cohorts.

OBJECTIVE: To investigate the relationships between the A-G point mutation at position -3826 bp in the 5' flanking domain of the uncoupling protein 1 (UCP1 A-3826G) and some obesity phenotypes in the Swedish Obese Subjects (SOS) cohorts of obese and non-obese men and women. Previous studies have supported the hypothesis of an association between the UCP1 A-3826G polymorphism and body weight regulation in humans. DESIGN: Case-control study comparing obese subjects from the SOS registry and a sample of the Swedish general population (body mass index (BMI) <27 kg/m2) with respect to genotype and allele frequencies of the UCP1 A-3826G polymorphism. SUBJECTS: A total of 985 Swedish subjects including 674 obese (310 Male; 364 Female) and 311 non-obese subjects (54 Male; 257 Female) from the SOS cohorts. MEASUREMENTS: DNA was extracted from total blood and genotyped by PCR-RFLP. Obesity-related phenotypes include weight history for SOS obese cohort and current weight, BMI, waist circumference and waist to hip ratio (WHR) for obese and normal weight subjects. RESULTS: No significant difference in the allelic frequencies between obese and non-obese subjects (0.25 vs 0.24; P = 0.67). In both genders, current weight, BMI, waist circumference, WHR and weight gain over time (either measures of maximal weight ever achieved minus weight at 20 y or current weight minus weight at 20 y) were similar in carriers and non-carriers of the UCP1 A-3826G mutation (P>0.05). Similar results were obtained when the three genotypes were compared. CONCLUSIONS: In contrast to what was found in other populations, the UCP1 A-3826G sequence variation is not associated with obesity-related phenotypes and weight gain over time in subjects from the SOS cohorts.

Adult↗

PubMed2004

Hypothalamic neuronal histamine regulates sympathetic nerve activity and expression of uncoupling protein 1 mRNA in brown adipose tissue in rats.

To clarify how hypothalamic neuronal histamine regulates peripheral energy expenditure, we investigated the effect of infusion of histamine into the third cerebral ventricle or discrete hypothalamic regions on sympathetic nerve activity and expression of uncoupling protein 1 (UCP1) mRNA in brown adipose tissue (BAT). Infusion of histamine (200 nmol) into the third cerebral ventricle of anesthetized rats significantly increased the electrophysiological activity of sympathetic nerves (P<0.01) and UCP1 mRNA expression in the BAT (P<0.05). Microinjection of histamine (10 nmol) into the paraventricular nucleus (PVN) and preoptic area (POA) produced similar significant increases in BAT sympathetic nerve activity (P<0.01 for each). By contrast, injection of histamine into the ventromedial hypothalamic nucleus or lateral hypothalamic area had no effect. We conclude that hypothalamic neuronal histamine may regulate energy expenditure in BAT through the activation of sympathetic nerves. The PVN and/or POA appear to be the principal hypothalamic sites that mediate the stimulatory effect of histamine on this efferent pathway.

Action Potentials↗

PubMed2005

The activities of antioxidant enzymes and monoamine oxidase and uncoupling protein 1 content in brown fat of hypo- and hyperthyroid rats.

We have studied the activities of antioxidant enzymes (AOE), namely, copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and catalase (CAT), and the activity of catecholamine-degrading enzyme monoamine oxidase (MAO) and uncoupling protein 1 (UCP1) content in brown fat (BF) of hypo- and hyperthyroid rats. We found that hypothyroidism decreased BF UCP1 content and increased MAO, MnSOD, and CAT activities. T3 increased UCP1 content and MnSOD activity and decreased CuZnSOD, MAO, and CAT activities, while T4 significantly altered (decreased) only CAT activity. This study shows that UCP1 content and MAO and AOE activities in rat BF are notably affected by changed thyroid status.

Adipose Tissue, Brown↗

PubMed2005

Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization in brown adipose tissue.

Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the beta-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial uncoupling protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.

Adipose Tissue, Brown↗

PubMed2003

Repeated immobilization stress increases uncoupling protein 1 expression and activity in Wistar rats.

Repeat immobilization-stressed rats are leaner and have improved cold tolerance due to enhancement of brown adipose tissue (BAT) thermogenesis. This process likely involves stress-induced sympathetic nervous system activation and adrenocortical hormone release, which dynamically enhances and suppresses uncoupling protein 1 (UCP1) function, respectively. To investigate whether repeated immobilization influences UCP1 thermogenic properties, we assessed UCP1 mRNA, protein expression, and activity (GDP binding) in BAT from immobilization-naive or repeatedly immobilized rats (3 h daily for 4 weeks) and sham operated or adrenalectomized (ADX) rats. UCP1 properties were assessed before (basal) and after exposure to 3 h of acute immobilization. Basal levels of GDP binding and UCP1 expression was significantly increased (140 and 140%) in the repeated immobilized group. Acute immobilization increased GDP binding in both naive (180%) and repeated immobilized groups (220%) without changing UCP1 expression. In ADX rats, basal GDP binding and UCP1 gene expression significantly increased (140 and 110%), and acute immobilization induced further increase. These data demonstrate that repeated immobilization resulted in enhanced UCP1 function, suggesting that enhanced BAT thermogenesis contributes to lower body weight gain through excess energy loss and an improved ability to maintain body temperature during cold exposure.

Adipose Tissue, Brown↗

PubMed2005

Uncoupling protein 1 in fish uncovers an ancient evolutionary history of mammalian nonshivering thermogenesis.

Uncoupling proteins (UCPs) increase proton leakage across the inner mitochondrial membrane. Thereby, UCP1 in brown adipose tissue dissipates proton motive force as heat. This mechanism of nonshivering thermogenesis is considered as a monophyletic trait of endothermic placental mammals that emerged about 140 million years ago and provided a crucial advantage for life in the cold. The paralogues UCP2 and UCP3 are probably not thermogenic proteins but convey mild uncoupling, which may serve to reduce the rate of mitochondrial reactive oxygen species production. Both are present in endotherms (mammals and birds), but so far only UCP2 has been identified in ectothermic vertebrates (fish and amphibia). The evolution of UCPs is of general interest in the search for the origin of mammalian UCP1-mediated nonshivering thermogenesis. We here show the presence of UCP1 and UCP3 in ectothermic teleost fish species using comparative genomics, phylogenetic inference, and gene expression analysis. In the common carp (Cyprinus carpio), UCP1 is predominantly expressed in the liver and strongly diminished in response to cold exposure, thus contrasting the cold-induced expression of mammalian UCP1 in brown adipose tissue. UCP3 mRNA is only found in carp skeletal muscle with expression levels increased fivefold in response to fasting. Our findings disprove the monophyletic nature of UCP1 in placental mammals and demonstrate that all three members of the core UCP family were already present before the divergence of ray-finned and lobe-finned vertebrate lineages about 420 million years ago.

Amino Acid Sequence↗

PubMed2000

Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on long-term body weight change in Finnish type 2 diabetic and non-diabetic control subjects.

OBJECTIVE: To investigate the independent and combined effects of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3AR) gene and the (-3826) A-->G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10y follow-up study. DESIGN: Controlled 10y follow-up study with baseline, 5 and 10y examinations. SUBJECTS: 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA1c. Genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: No significant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n = 103; change in weight 6.5 +/- 2.5% vs -0.2 +/- 0.8%, P=0.036, and change in Body Mass Index 8.5 +/- 2.6% vs 2.0 +/- 0.8%, P= 0.060, mean +/- s.e.m.). CONCLUSIONS: The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.

Anthropometry↗

PubMed1998

Different regulation of free fatty acid levels and glucose oxidation by the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and the promoter variant (A-3826G) of the uncoupling protein 1 gene in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is characterized by variable expression of dyslipidemias and insulin resistance. Because the genetic background for FCHL is unknown, we investigated the effect of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and the promoter variant A --> G (-3826) of the uncoupling protein 1 (UCP1) gene on glucose and lipid metabolism in FCHL families. Both polymorphisms were screened in 228 members from 27 families with FCHL and in 82 control men from a random population sample. The frequency of the polymorphisms of the beta3-AR and UCP1 genes did not differ between patients with FCHL and controls. Although the rate of insulin-stimulated whole-body glucose uptake evaluated by the euglycemic clamp in family members of patients with FCHL was unaffected by both polymorphisms, subjects with the Trp64Arg genotype of the beta3-AR gene had higher rates of glucose oxidation (17.6+/-4.5 v 15.8+/-4.1 micromol/kg/min, P=.017) and lower levels of free fatty acids (FFAs) in the fasting state (0.56+/-0.27 v 0.61+/-0.28 mmol/L, P=.027) and during the euglycemic clamp (0.12+/-0.10 v 0.21+/-0.15 mmol/L, P=.041) than subjects with the Trp64Trp genotype. We conclude that in FCHL families, codon 64 polymorphism of the beta3-AR gene may influence the rate of glucose oxidation via FFA levels.

Abdomen↗

PubMed2006

The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets.

Piglets appear to lack brown adipose tissue, a specific type of fat that is essential for nonshivering thermogenesis in mammals, and they rely on shivering as the main mechanism for thermoregulation. Here we provide a genetic explanation for the poor thermoregulation in pigs as we demonstrate that the gene for uncoupling protein 1 (UCP1) was disrupted in the pig lineage. UCP1 is exclusively expressed in brown adipose tissue and plays a crucial role for thermogenesis by uncoupling oxidative phosphorylation. We used long-range PCR and genome walking to determine the complete genome sequence of pig UCP1. An alignment with human UCP1 revealed that exons 3 to 5 were eliminated by a deletion in the pig sequence. The presence of this deletion was confirmed in all tested domestic pigs, as well as in European wild boars, Bornean bearded pigs, wart hogs, and red river hogs. Three additional disrupting mutations were detected in the remaining exons. Furthermore, the rate of nonsynonymous substitutions was clearly elevated in the pig sequence compared with the corresponding sequences in humans, cattle, and mice, and we used this increased rate to estimate that UCP1 was disrupted about 20 million years ago.

Animals↗

PubMed2007

Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism.

Obesity-related increase in body fat mass is a risk factor for many diseases, including type 2 diabetes. Controlling adiposity by targeted modulation of adipocyte enzymes could offer an attractive alternative to current dietary approaches. Brown adipose tissue, which is present in rodents but not in adult humans, expresses the mitochondrial uncoupling protein 1 (UCP1) that promotes cellular energy dissipation as heat. Here, we report on the direct metabolic effects of forced UCP1 expression in white adipocytes derived from a murine (3T3-L1) preadipocyte cell line. After stable integration, the ucp1 gene product was continuously expressed during differentiation and reduced the total lipid accumulation by approximately 30% without affecting other adipocyte markers, such as cytosolic glycerol-3-phosphate dehydrogenase activity and leptin production. The expression of UCP1 also decreased glycerol output and increased glucose uptake, lactate output, and the sensitivity of cellular ATP content to nutrient removal. However, oxygen consumption and beta-oxidation were minimally affected. Together, our results suggest that the reduction in intracellular lipid by constitutive expression of UCP1 reflects a downregulation of fat synthesis rather than an upregulation of fatty acid oxidation.

3T3-L1 Cells↗