Impact of dietary protein content on uncoupling protein mRNA abundance in swine

The present study was designed to determine if dietary protein can alter uncoupling protein (UCP) expression in swine, as has been shown in rats, and attempt to identify the mechanism. Eight pigs (~ 50 kg body mass) were fed an 18% crude protein (CP) diet while another eight pigs were switched to a diet containing 12% crude protein (CP) and fed these diets until 110 kg body mass. The outer (OSQ) and middle (MSQ) subcutaneous adipose tissues, liver, leaf fat, longissimus (LM), red portion of the semitendinosus (STR) and the white portion of the ST (STW) were analyzed for gene expression by real-time PCR. Feeding of 12% CP did not alter growth or carcass composition, relative to 18% CP (P > 0.05). Serum growth hormone, non-esterified fatty acids, triglycerides and urea nitrogen were reduced with the feeding of 12% CP (P < 0.05). The UCP2 mRNA abundance was reduced in LM, STR, MSQ and OSQ with feeding of 12% CP (P < 0.05), as was UCP3 mRNA abundance in MSQ and STW (P < 0.01). Peroxisome proliferation activated receptor α (PPARα) and PPARγ were reduced in MSQ and STR (P < 0.05) with feeding 12% CP as was the PPARα regulated protein, acyl CoA oxidase (ACOX, P < 0.05). These data suggest that feeding 12% CP relative to 18% CP reduces serum NEFA, which reduces PPARα and PPARγ expression and consequently reduces UCP2 lipoperoxidation in OSQ and STR and also reduced UCP3 associated fatty acid transport in MSQ and STW.     

Differential effects of thyroid hormone manipulation and �� adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T₃) in on the first day of life. T₃ and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective β3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T₃ (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T₃ administration raised plasma T₃ concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets (p = 0.042) and was downregulated following T₃ administration (p = 0.014). Irrespective of genotype, ZD increased UCP2 mRNA abundance (Meishan p = 0.05, commercial p = 0.03). Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets.Key words: mitochondria, postnatal growth, metabolism     

Systemic administration of epidermal growth factor increases UCP3 mRNA levels in skeletal muscle and adipose tissue in rats

We have previously reported that systemic epidermal growth factor (EGF) treatment in rats reduces the amount of adipose tissue despite an unaltered food intake. The mitochondrial uncoupling proteins (UCP2 and UCP3) are thought to uncouple the respiratory chain and thus to increase energy expenditure. In order to find out whether the UCP system was involved in the EGF-induced weight loss, the effects of EGF on UCP2 and UCP3 in adipose tissue and skeletal muscle were investigated in the present study. Eight rats were treated with placebo or EGF (150 microg/kg/day) for seven days via mini-osmotic pumps. The EGF-treated rats gained significantly less body weight during the study period than the placebo-treated animals and had significantly less adipose tissue despite a similar food intake. The placebo group and the EGF group had similar UCP2 mRNA expression (in both adipose tissue and skeletal muscle), whereas the EGF-treated group compared to the placebo group had significantly higher UCP3 mRNA expression in both skeletal muscle (3.76 +/- 0.90 vs 8.41 +/- 0.87, P < 0.05) and in adipose tissue (6.38 +/- 0.71 vs 12.48 +/- 1.79, P < 0.05). In vitro studies with adipose tissue fragments indicated that the EGF effect probably is mediated indirectly as incubations with EGF (10 microM) were unable to affect adipose tissue UCP expression, whereas incubations with bromopalmitate stimulated both UCP2 and UCP3 mRNA expression twofold. Thus, EGF treatment in vivo was found to enhance UCP3 mRNA expression in both adipose tissue and skeletal muscle, which may indicate that the EGF effect on body composition might involve up-regulation of UCP3 in skeletal muscle and adipose tissue.     

Changes in the expression of uncoupling proteins and lipases in porcine adipose tissue and skeletal muscle during feed deprivation*(1)

The hormone-sensitive and lipoprotein lipases are critical determinants of the metabolic adaptation to starvation. Additionally, the uncoupling proteins have emerged with potential roles in the metabolic adaptations required by energy deficiency. The objective of this study was to evaluate the expression (mRNA abundance) of uncoupling proteins 2 and 3 and that of hormone-sensitive and lipoprotein lipase in the adipose tissue and skeletal muscle of the pig in relationship to feed deprivation. Thirty-two male castrates (87 kg +/- 5%) were assigned at random to fed and feed-deprived treatment groups. After 96 hr, the pigs were euthanized and adipose and skeletal muscle tissue obtained for total RNA extraction and nuclease protection assays. Feed deprivation increased uncoupling protein 3 mRNA abundance 103-237% (P < 0.01) in longissimus and red and white semitendinosus muscle. In contrast, the increase in uncoupling protein 3 mRNA in adipose tissue was only 23% (P < 0.06), and adipose uncoupling protein 2 mRNA was not influenced (P > 0.66) by feed deprivation. The increased abundance of uncoupling protein 2 mRNA in the longissimus muscle of feed-deprived pigs was small (22%), but significant (P < 0.04). The expression of hormone-sensitive lipase was increased 46% and 64% (P < 0.04) in adipose tissue and longissimus muscle, respectively, by feed deprivation, whereas adipose lipoprotein lipase expression was reduced (P < 0.01) to 20% of that of the fed group. Longissimus lipoprotein lipase expression in the feed-deprived group was 37% of that of the fed group (P < 0.01), and similar reductions were detected in red and white semitendinosus muscle. Overall, these findings indicate that uncoupling protein 3 expression in skeletal muscle is quite sensitive to starvation in the pig, whereas uncoupling protein 2 changes are minimal. Furthermore, we conclude that hormone-sensitive lipase is upregulated at the mRNA level with prolonged feed deprivation, whereas lipoprotein lipase is downregulated.     

Differential effects of thyroid hormone manipulation and β adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T₃) in on the first day of life. T₃ and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective β3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T₃ (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T₃ administration raised plasma T₃ concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets and was downregulated following T₃ administration. Irrespective of genotype, ZD increased UCP2 mRNA abundance. Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets.     

Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue. Unaltered iodothyronine 5'-deiodinase activity is necessary for the response to environmental temperature at birth

We have performed a sequential study on the abundance of the mRNA for uncoupling protein (UCP), subunit II of cytochrome-c oxidase (COII) and lipoprotein lipase in brown adipose tissue during the fetal and postnatal periods. Moreover, we have determined whether these parameters can be modulated by ambient temperature in the early hours after birth, and at which point in development this sensitivity first appears. UCP gene expression in the fetal and neonatal period has particular features when compared with overall mitochondriogenesis (COII mRNA expression) or with the expression of lipoprotein lipase mRNA. There is a specific induction of UCP gene expression between days 18 and 19 of pregnancy followed by a specific increase of UCP gene expression in utero and a further increase after birth. The acquisition of the physiological apparatus capable of the response to UCP and lipoprotein lipase gene expression to the environmental temperature is not achieved until the last day of fetal development. This result suggests that mechanisms of beta-adrenergic modulation of gene expression in brown fat are already established at birth. From an experiment on iopanoic acid treatment of pregnant mothers, it was concluded that iodothyronine 5'-deiodinase activity is not necessary for the expression of the mRNAs for UCP, COII and lipoprotein lipase in the fetus whereas it is necessary for the acquisition of temperature sensitivity to these parameters at birth.     

Human Uncoupling Proteins and Obesity

SCHRAUWEN, PATRICK, KEN WALDER, AND ERIC RAVUSSIN. Human coupling proteins and obesity. Obes. Res. 1999;7:97–105. Uncoupling protein (UCP) 2 and UCP3 are newly discovered proteins that can uncouple ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting energy metabolism efficiency. In contrast to UCP1, which is only present in brown adipose tissue, UCP2 has a wide tissue distribution, whereas UCP3 is expressed predominantly in skeletal muscle. Some evidence of a role for UCPs in modulating metabolic rate was provided by linkage and association studies. Furthermore, UCP3 gene expression was found to correlate negatively with body mass index and positively with sleeping metabolic rate in Pima Indians. Treatment with thyroid hormone increases expression of the UCP2 and UCP3 genes. Other regulators of UCP2 and UCP3 gene expression are β₃-adrenergic agonists and glucocorticoids. Surprisingly, fasting has a stimulatory effect on UCP2 and UCP3 mRNA levels, possibly explained by the effects of free fatty acid on UCP2 and UCP3 gene expression.     

Role of the beta(3)-adrenergic receptor and/or a putative beta(4)-adrenergic receptor on the expression of uncoupling proteins and peroxisome proliferator-activated receptor-gamma coactivator-1.

Administration of beta-adrenergic receptor (beta-AR) agonists, especially beta(3)-AR agonists, is well known to increase thermogenesis in rodents and humans. In this work we studied the role of the beta(3)-AR in regulating mRNA expression of genes involved in thermogenesis, i.e., mitochondrial uncoupling proteins UCP2 and UCP3, and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1), in mouse skeletal muscle. For this purpose, different beta(3)-AR agonists were administered acutely to both wild type mice and mice whose beta(3)-AR gene has been disrupted (beta(3)-AR KO mice). CL 316243 increased the expression of UCP2, UCP3 and PGC-1 in wild type mice only. By contrast, BRL 37344 and CGP 12177 increased the expression of UCP2 and UCP3 in both wild type and beta(3)-AR KO mice, whereas they increased the expression of PGC-1 in wild type mice only. Finally, acute (3 h) cold exposure increased the expression of UCP2 and UCP3, but not PGC-1, in skeletal muscle of both wild type and beta(3)-AR KO mice. These results show that selective stimulation of the beta(3)-AR affects the expression of UCP2, UCP3 and PGC-1 in skeletal muscle. This effect is probably indirect, as muscle does not seem to express beta(3)-AR. In addition, our data suggest that BRL 37344 and CGP 12177 act, in part, through an as yet unidentified receptor, possibly a beta(4)-AR.     

Immortal brown adipocytes from p53-knockout mice: differentiation and expression of uncoupling proteins

Brown adipose tissue (BAT) is the specific site for metabolic heat production in mammals. To establish a novel immortal brown adipocyte cell line, the stromal-vascular fraction containing preadipocytes was obtained from interscapular BAT of mice deficient of a tumor-suppressor gene p53. The p53-deficient cells, tentatively named as HB2 cells, could be cultured in vitro after repeated passages and differentiated into adipocytes in the presence of insulin, T3 and/or troglitazone, expressing some adipocyte-specific genes and accumulating intracellular lipid droplets. The mRNA level of uncoupling protein 1 (UCP1), a mitochondrial protein specifically present in brown adipocytes, was undetectable in HB2 preadipocytes, but increased after adipose differentiation. In HB2 adipocytes, UCP1 mRNA expression was markedly activated after stimulation of the beta-adrenergic receptor pathway. The mRNA of UCP2 and UCP3, recently cloned isoforms of UCP1, were also detected in HB2 adipocytes, but their levels were not influenced by adrenergic stimulation. Thus HB2 cells seem useful for in vitro studies of BAT and UCP functions.     

Muscle-specific up-regulation of rat UCP3 mRNA expression by long-term hindlimb unloading

The effect of long-term hindlimb unloading (2 or 5 week) on the expression of uncoupling protein-3 (UCP3) gene was investigated in rat skeletal muscles. The interaction of hindlimb unloading and thyroid status was also investigated at 2 weeks. Whatever the duration, mechanical unloading induced a similar increase in UCP3 mRNA relative abundance in the slow-twitch soleus (SOL) muscle (+80%, P < 0.05), whereas no effect was observed in the fast-twitch extensor digitorum longus (EDL) muscle. Hypothyroidism down-regulated while hyperthyroidism up-regulated UCP3 mRNA relative abundance in both SOL and EDL muscles, but thyroid status did not prevent the up-regulation of UCP3 induced by 2 weeks of suspension. These data therefore indicate for the first time that long-term hindlimb unloading up-regulates muscle UCP3 gene expression in a muscle-specific manner which is independent of thyroid status.     

Development of Phodopus sungorus brown preadipocytes in primary cell culture: effect of an atypical beta-adrenergic agonist, insulin, and triiodothyronine on differentiation, mitochondrial development, and expression of the uncoupling protein UCP

A new cellular model for the study of brown adipocyte development and differentiation in vitro is presented. Preadipocytes isolated from brown adipose tissue (BAT) of the djungarian dwarf hamster Phodopus sungorus are able to proliferate and differentiate in vitro into true brown adipocytes able to express the BAT marker protein the uncoupling protein (UCP). Whereas basal UCP expression is very low, its mRNA levels as well as the UCP detected by immunoblotting are highly increased by beta-adrenergic stimulation. The novel, atypical beta-adrenergic compound D7114 (ICI Pharmaceuticals, Macclesfield, Cheshire, England) was found to increase the number of adipocytes as well as UCP mRNA and UCP content of mitochondria, indicating the involvement of an atypical or beta 3 receptor. Insulin was found to play an important role in brown adipocyte differentiation and mitochondrial development, whereas T3 seemed to be implicated more directly in UCP expression. In a defined, serum-free medium a synergistic stimulatory action of insulin and T3 on UCP expression was found, which seems to involve a pathway different from that of beta-adrenergic UCP stimulation.     

Influence of size at birth on the endocrine profiles and expression of uncoupling proteins in subcutaneous adipose tissue, lung, and muscle of neonatal pigs

Epidemiological studies suggest that infants of low birth weight show poor neonatal growth and increased susceptibility to adult diseases such as diabetes and lung disease. Uncoupling protein 2 and 3 (UCP2 and UCP3) have been implicated in the development of such diseases; pigs provide an ideal model to examine the influence of birth weight due to the natural variance in piglet weight within a litter. This study examined whether birth weight influences the expression of UCP2 and UCP3 in adipose tissue, skeletal muscle, and lung. Piglets from 11 litters were ranked according to birth weight and three from each litter assigned to small (SFD), normal (NFD), or large for dates (LFD) groups. Blood samples and morphometric measurements were taken over the first 14 days of life, and tissue samples were taken on day 7 or 14. Plasma hormone and metabolite concentrations and the expression of UCP2 and UCP3 mRNA in adipose tissue, skeletal muscle, and lung were measured. UCP2 and UCP3 expression in adipose tissue was lower in the SFD compared with the LFD group on day 7. UCP3 expression in skeletal muscle was higher than that of adipose tissue. Lung UCP2 and skeletal muscle UCP3 mRNA expression were unaffected by size at birth. Regression analysis indicated that UCP3 expression was differentially associated with IGF-1, leptin, and insulin. In conclusion, low birth weight is associated with tissue-specific effects on UCP expression. It remains to be established whether these subsequently contribute to pathological conditions such as diabetes.     

禁食及胰岛素水平对大鼠解偶联蛋白-1、2、3基因表达的影响

 为探讨禁食和胰岛素对解偶联蛋白 - 1、2、3基因 (UCP1 ,2 ,3)表达的影响 ,应用 RT- PCR方法观察了在不同禁食时间和应用胰岛素条件下大鼠白色脂肪组织、棕色脂肪组织和骨骼肌中 UCP1 ,2 ,3m RNA水平的变化 .UCP1基因只在大鼠棕色脂肪组织中表达 .UCP2 ,3基因在三种组织中均有表达 ,在白色脂肪组织中以 UCP2表达为主 ;在骨骼肌中以 UCP3表达为主 .过夜禁食使棕色脂肪组织 UCP1 ,3m RNA水平明显下降 (P<0 .0 1 ) ;UCP2 m RNA水平在三种组织中均呈上升反应 ,以白色脂肪组织中表现最为明显 (P<0 .0 5) ;而对白色脂肪组织和骨骼肌中 UCP3基因表达无明显影响 .禁食时间延长至 48h,除棕色脂肪组织中 UCP2 ,3基因有明显下降外 ,各组织中UCPs基因表达基本调节至正常或高于对照组水平 .胰岛素对 UCPs基因表达水平有一定的上调作用 ,这一作用对棕色脂肪组织 UCPs各基因及骨骼肌中 UCP3基因表现得尤为明显 (P<0 .0 5) .大鼠 UCPs基因表达有一定的组织特异性 ;禁食时间对三种组织中 UCPs各成员基因表达的影响有时相上的区别 ;胰岛素可以调 UCPs各成员基因的表达 .结果反映了 UCPs各成员在能量代谢调节上的不同作用 ,这为理解膳食 -产热与体重调节的关系 ,及其能量代谢平衡与疾病关系提供了实验依据     

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.     

Developmental patterns of serum leptin levels, leptin gene expression in adipose tissue and Ob-Rb gene expression in hypothalamus of Erhualian and Large White pigs

~~Developmental patterns of serum leptin levels, leptin gene expression in adipose tissue and Ob-Rb gene expression in hypothalamus of Erhualian and Large White pigs~~     

n-3 PUFA attenuate lipopolysaccharide-induced down-regulation of toll-like receptor 4 expression in porcine adipose tissue but does not alter the expression of other immune modulators

The objective of this study was to test the hypothesis that the inflammatory response to lipopolysaccharide (LPS) in vivo is accompanied by down-regulation of toll-like receptor (TLR) 4 in adipose tissue, and a source of protected n-3 polyunsaturated fatty acid (PUFA) attenuates this response. Seventy-two castrated male pigs were individually fed either a control (CONT) diet, or the CONT diet containing 1.87% (LF) or 7.50% (HF) protected n-3 PUFA on a weight basis for 7 weeks. Adipose and muscle tissue biopsy samples were taken at Weeks 1, 2, 3, 4 and 7 to assess gene expression and/or confirm tissue enrichment with eicosapentaenoic acid and docosahexaenoic acid and reflected the n-3 PUFA contained in the diet. The LPS challenge was performed at week 7 and consisted of sequential injections of 10 and 2.5 mug LPS per kilogram of body weight 23 h apart. The LPS challenge resulted in a marked down-regulation (P=.004) of TLR4 at the protein level in the adipose tissue of challenged vs. control pigs, but LF and HF clearly blocked this response at the mRNA level. Although LF and HF also attenuated (P<.001) the LPS-induced acute febrile response and lowered (P<.002) serum concentrations of tumour necrosis factor alpha. Cyclooxygenase 2 and 12-lipoxygenase were readily expressed in porcine adipose tissue, but there was no effect of LF, HF or LPS on expression levels of these inflammatory mediators, or that of TNF and interleukin 6, at the conclusion of the challenge period. These findings indicate that adipose tissue responds to LPS administration in vivo by reducing TLR4 mRNA and protein abundance and that the anti-inflammatory effects of n-3 PUFA do not include down-regulation of TLR4 in adipose tissue.     

皖南花猪不同发育阶段脂肪组织脂联素及受体和瘦素mRNA的变化

目的:研究皖南花猪不同发育阶段不同部位脂肪组织中脂联素(Adp)及其受体(AdpR1、AdpR2)和瘦素(leptin)mRNA的变化及性别差异。方法:选择出生、30、45、90、180日龄的皖南花猪雌、雄各5头,以β-actin为内标,采用△△Ct相对定量实时荧光PCR方法对皮下脂肪和肾周脂肪中Adp、AdpR1、AdpR2和leptin mRNA进行定量分析。结果:不同发育阶段皮下脂肪和肾周脂肪Adp、AdpR1、AdpR2、leptin mRNA的表达都有极显著差异(P<0.01)。总体上Adp mRNA在肾周脂肪显著高于皮下脂肪(P<0.05);AdpR1、AdpR2和leptin mRNA在皮下脂肪显著或极显著高于肾周脂肪(P<0.05或P<0.01)。除个别基因和个别日龄外,总体上各基因mRNA表达的性别差异不明显。无论在皮下脂肪还是肾周脂肪,Adp mRNA的表达与AdpR1、AdpR2呈显著或极显著正相关(P<0.05或P<0.01),与leptin显著负相关(P<0.05)。结论:皖南花猪不同发育阶段脂肪组织中Adp、AdpR1、AdpR2、leptin的基因表达有差异,且有组织特异性;Adp与其受体mRNA表达有相关性。     

解偶联蛋白基因-3826多态性与其mRNA表达相关性的研究

为了探讨解偶联蛋白（ＵＣＰ）基因－３８２６多态性与ＵＣＰｍＲＮＡ表达水平之间可能存在的联系,应用ＲＴ－ＰＣＲ方法测定了ＵＣＰ基因－３８２６多态性野生型（ＡＡ）,杂合子（ＡＧ）和突变纯合子（ＧＧ）３组人群脂肪组织中ＵＣＰｍＲＮＡ的表达水平．定量结果指出：３种基因型（ＡＡ、ＡＧ和ＧＧ）携带者腹膜内脂肪的ＵＣＰｍＲＮＡ表达水平存在极显著差异（Ｐ＜０．０１）,并显示突变等位基因（Ｇ）的数量与ＵＣＰｍＲＮＡ表达水平呈负相关．此结果表明ＵＣＰ基因Ａ→Ｇ（－３８２６）变异与ＵＣＰｍＲＮＡ表达水平降低密切相关．但该变异导致ＵＣＰｍＲＮＡ表达水平降低的机制还有待进一步研究     

The control of UCP1 is dissociated from that of PGC-1alpha or of mitochondriogenesis as revealed by a study using beta-less mouse brown adipocytes in culture

In rodent brown adipose tissue, the beta-adrenergic signaling is believed, by an action on PGC-1alpha, to control UCP1 expression and mitochondriogenesis. We addressed this hypothesis using beta(1)/beta(2)/beta(3)-adrenoceptor knockout (beta-less) brown adipocytes in primary culture. In these cells: (a) proliferation and differentiation into multilocular cells were normal; (b) UCP1 mRNA expression was dramatically decreased (by 93%), whereas PGC-1alpha and mtTFA mRNA expressions were not; (c) UCP1, PGC-1alpha and COX IV protein expressions were decreased by 97%, 62% and 22%, respectively. Altogether the data show a dissociation between the control of UCP1, which is mostly beta-adrenoceptor-dependent and that of PGC-1alpha and of mitochondriogenesis which are not.