棕色脂肪组织特异性基因在抵抗肥胖中作用的研究
|
摘要
目的:研究高脂饮食诱导肥胖大鼠与肥胖抵抗大鼠肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2表达情况,探讨棕色脂肪组织中特异性基因表达与高脂饮食诱导肥胖及肥胖抵抗的关系。
方法:40只雄性SD大鼠,按体重随机分为高脂实验组(n=28)和基础对照组(n=12)。分别给予高脂饲料和基础饲料喂养。高脂饮食5周末根据体重将高脂实验组再分为饮食诱导肥胖组(DIO,n=6)和饮食诱导肥胖抵抗组(DIO-R,n=6),与基础对照组(n=6)比较各组大鼠体重、两种脂肪重水平,使用实时荧光定量PCR及Western blot方法比较三组肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2表达水平的差异。
结果:DIO组大鼠附睾、肾周白色脂肪组织重明显高于DIO-R与对照组大鼠,DIO-R大鼠肩胛间棕色脂肪组织重及Dio-2、PGC-1α、UCP-1mRNA表达水平明显高于DIO大鼠(P<0.05)。高脂组大鼠PGC-1α、Dio-2mRNA表达水平均低于对照组大鼠(P<0.05);DIO-R组大鼠UCP-1 mRNA表达水平高于对照组大鼠(P<0.05)。DIO大鼠UCP-1蛋白水平表达低于基础对照组及DIO-R大鼠(P<0.05)。
结论:高脂饮食条件下,SD大鼠表现为明显的肥胖易感性差异。饮食诱导肥胖抵抗大鼠棕色脂肪组织重及特异性基因表达升高,能通过增加能量消耗而抵抗肥胖。棕色脂肪组织特异性基因表达在抵抗肥胖中有重要作用。
目的:研究电针刺激对肥胖大鼠肩胛间棕色脂肪组织中UCP-1、PGC-1α表达的影响,探讨电针刺激对饮食所致肥胖减肥的机制。
方法:40只雄性SD大鼠,随机分为高脂实验组(n=28)和基础对照组(n=12),分别给予高脂饲料和基础饲料喂养。高脂饮食5周末,将高脂实验组大鼠体重大于对照组最大体重者为饮食诱导肥胖大鼠,随机分为两组:肥胖组(DIO,n=5)、电针刺激组(EA组,n=5)。基础饮食大鼠随机取5只作为基础对照组(n=5)。基础饲料适应性喂养一周后,其中EA组选取足三里、三阴交给予电针刺激,每周三次,每次半小时,观察摄食量及体重变化,6周后使用实时荧光定量PCR及Western blot方法比较三组大鼠棕色脂肪组织中UCP-1、PGC-1α表达水平的差异。
结果:电针刺激6周后,电针刺激组大鼠棕色脂肪组织中UCP-1、PGC-1αmRNA及蛋白水平表达均高于DIO组及对照组(P<0.05),电针刺激组大鼠体重、摄食量低于肥胖组大鼠(P<0.05)。
结论:电针刺激增加了棕色脂肪组织特异性基因表达,减少摄食量,从而抵抗肥胖。
Objective: To study the brown adipose tissue (BAT) characteristic genes expression in diet-induced obesity-resistant (DIO-R) and diet-induced obesity (DIO) rats .
Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into control group and high-fat group and they were fed with basic diet and high-fat diet respectively for 5 weeks. DIO-R and DIO rats were selected according to their body weight, then the intake of diet and body fat contents were measured, the expression levels of BAT specific genes were determined by real-time PCR and western blot.
Results: The results showed that the body weight, pararenal or epididymal white fat tissue in DIO-R rats were significantly lower than those of DIO rats ( P < 0.05) . Meanwhile, the interscapular BAT of DIO-R rats was higher compared to DIO rats( P < 0.05) . The expression of UCP-1,PGC-1αand Dio-2 mRNA of interscapular BAT in DIO-R rats were higher than that of DIO rats( P < 0.05). The PGC-1α、Dio-2 mRNA levels of rats in high-fat diet group were lower compared to basic diet group,while UCP-1 mRNA levels were higher.( P < 0.05). The UCP-1 protein levels of BAT in DIO rats were lower than that of other two groups(P<0.05).
Conclusion: High fat diets can induce SD rats to develop obesity and obesity-resistance. The BAT characteristic genes may play important role in resisting diet-induced obesity of rats.
Objective: To explore the effects of acupuncture on expression of characteristic genes in interscapular brown adipose tissue, and elucidate mechanisms of acupuncture in slimming.
Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into 2 groups: basic group (n=12) and high-fat group(n=28) , they were fed with basic diet and high-fat diet respectively. After 5 weeks, diet-induced obesity (DIO) rats were selected according to their body weight from the high-fat group, and then divided into 2 groups: obesity group(DIO,n=5), acupuncture group(EA,n=5) .5 rats were selected randomly from basic group as control group.3 groups were all given basic diet for 1 week, and then acupuncture with electric on“Housanli”(ST 36) and“Sanyinjiao”(SP 6) of the EA group rats, with left and right interchange, 30mins each time and 3 times a week for 6 weeks. The weight of rats, fat weight around the kidney , intake of diet and expression levels of BAT specific genes between 3 groups were compared.
Results: After 6 weeks of acupuncture, the expression of UCP-1 and PGC-1αmRNA and protein in interscapular BAT of EA group rats were higher than those of obesity rats and control group(P < 0.05).The body weight, intake of diet of EA group rats were significantly lower compared to obesity group rats (P < 0.05).
Conclusion: Acupuncture can increase expression of the BAT characteristic genes, reduce intake of diet and then resist obesity.
方法:40只雄性SD大鼠,按体重随机分为高脂实验组(n=28)和基础对照组(n=12)。分别给予高脂饲料和基础饲料喂养。高脂饮食5周末根据体重将高脂实验组再分为饮食诱导肥胖组(DIO,n=6)和饮食诱导肥胖抵抗组(DIO-R,n=6),与基础对照组(n=6)比较各组大鼠体重、两种脂肪重水平,使用实时荧光定量PCR及Western blot方法比较三组肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2表达水平的差异。
结果:DIO组大鼠附睾、肾周白色脂肪组织重明显高于DIO-R与对照组大鼠,DIO-R大鼠肩胛间棕色脂肪组织重及Dio-2、PGC-1α、UCP-1mRNA表达水平明显高于DIO大鼠(P<0.05)。高脂组大鼠PGC-1α、Dio-2mRNA表达水平均低于对照组大鼠(P<0.05);DIO-R组大鼠UCP-1 mRNA表达水平高于对照组大鼠(P<0.05)。DIO大鼠UCP-1蛋白水平表达低于基础对照组及DIO-R大鼠(P<0.05)。
结论:高脂饮食条件下,SD大鼠表现为明显的肥胖易感性差异。饮食诱导肥胖抵抗大鼠棕色脂肪组织重及特异性基因表达升高,能通过增加能量消耗而抵抗肥胖。棕色脂肪组织特异性基因表达在抵抗肥胖中有重要作用。
目的:研究电针刺激对肥胖大鼠肩胛间棕色脂肪组织中UCP-1、PGC-1α表达的影响,探讨电针刺激对饮食所致肥胖减肥的机制。
方法:40只雄性SD大鼠,随机分为高脂实验组(n=28)和基础对照组(n=12),分别给予高脂饲料和基础饲料喂养。高脂饮食5周末,将高脂实验组大鼠体重大于对照组最大体重者为饮食诱导肥胖大鼠,随机分为两组:肥胖组(DIO,n=5)、电针刺激组(EA组,n=5)。基础饮食大鼠随机取5只作为基础对照组(n=5)。基础饲料适应性喂养一周后,其中EA组选取足三里、三阴交给予电针刺激,每周三次,每次半小时,观察摄食量及体重变化,6周后使用实时荧光定量PCR及Western blot方法比较三组大鼠棕色脂肪组织中UCP-1、PGC-1α表达水平的差异。
结果:电针刺激6周后,电针刺激组大鼠棕色脂肪组织中UCP-1、PGC-1αmRNA及蛋白水平表达均高于DIO组及对照组(P<0.05),电针刺激组大鼠体重、摄食量低于肥胖组大鼠(P<0.05)。
结论:电针刺激增加了棕色脂肪组织特异性基因表达,减少摄食量,从而抵抗肥胖。
Objective: To study the brown adipose tissue (BAT) characteristic genes expression in diet-induced obesity-resistant (DIO-R) and diet-induced obesity (DIO) rats .
Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into control group and high-fat group and they were fed with basic diet and high-fat diet respectively for 5 weeks. DIO-R and DIO rats were selected according to their body weight, then the intake of diet and body fat contents were measured, the expression levels of BAT specific genes were determined by real-time PCR and western blot.
Results: The results showed that the body weight, pararenal or epididymal white fat tissue in DIO-R rats were significantly lower than those of DIO rats ( P < 0.05) . Meanwhile, the interscapular BAT of DIO-R rats was higher compared to DIO rats( P < 0.05) . The expression of UCP-1,PGC-1αand Dio-2 mRNA of interscapular BAT in DIO-R rats were higher than that of DIO rats( P < 0.05). The PGC-1α、Dio-2 mRNA levels of rats in high-fat diet group were lower compared to basic diet group,while UCP-1 mRNA levels were higher.( P < 0.05). The UCP-1 protein levels of BAT in DIO rats were lower than that of other two groups(P<0.05).
Conclusion: High fat diets can induce SD rats to develop obesity and obesity-resistance. The BAT characteristic genes may play important role in resisting diet-induced obesity of rats.
Objective: To explore the effects of acupuncture on expression of characteristic genes in interscapular brown adipose tissue, and elucidate mechanisms of acupuncture in slimming.
Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into 2 groups: basic group (n=12) and high-fat group(n=28) , they were fed with basic diet and high-fat diet respectively. After 5 weeks, diet-induced obesity (DIO) rats were selected according to their body weight from the high-fat group, and then divided into 2 groups: obesity group(DIO,n=5), acupuncture group(EA,n=5) .5 rats were selected randomly from basic group as control group.3 groups were all given basic diet for 1 week, and then acupuncture with electric on“Housanli”(ST 36) and“Sanyinjiao”(SP 6) of the EA group rats, with left and right interchange, 30mins each time and 3 times a week for 6 weeks. The weight of rats, fat weight around the kidney , intake of diet and expression levels of BAT specific genes between 3 groups were compared.
Results: After 6 weeks of acupuncture, the expression of UCP-1 and PGC-1αmRNA and protein in interscapular BAT of EA group rats were higher than those of obesity rats and control group(P < 0.05).The body weight, intake of diet of EA group rats were significantly lower compared to obesity group rats (P < 0.05).
Conclusion: Acupuncture can increase expression of the BAT characteristic genes, reduce intake of diet and then resist obesity.
引文
1. Cannon B, Nedergaard J. Brown adipose tissue function and physiological significance. Physiol Rev. 2004,84:277–3592
2. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev. 1984,64 (1): 1-64
3. Lin J, Wu PH, Tarr PT, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004,119:121-35.
4. Tiraby C, and Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol. Metab.2003, 14, 439–441.
5. Cinti S. Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ.J Endocrinol Invest.2002, 25(10):823-35.
6. Himms-Hagen J, Melnyk A, Zingaretti MC, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytesl. Am J Physiol CellPhysiol.2000, 279(3):C670-681.
7. Jimenez M, Barbatelli G, Allevi R, et al.β3-Adreno-ceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white fat. Eur J Biochem.2003, 270 (4): 699-705.
8. Kim DW, Kim BS, et al. Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells. Exp. Mol. Med. Vol. 2003,35(6), 518-526
9. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
10. Nedergaard J, Bengtsson T, and Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab.2007, 293:E444–E452.
11. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men.N Engl J Med. 2009,360:1500-8.
1. Haffner SM, Stern MP, et al. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990; 263: 2893-2898.
2. Levin BE, Hogan S, and Sullivan AC. Initiation and perpetuation of obesity and obesity resistance in rats. Am J Physiol Regulatory Integrative Comp Physiol 256: R766–R771,1989.
3. Tian DR, Li XD, Wang F, et al. Up-regulation of the expression of cocaine and amphetamine-regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats.Neurosci Lett 2005;383:17–21.
4. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009,360:1518-25.
5. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men.N Engl J Med. 2009,360:1500-8.
6. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev. 1984,64 (1): 1-64
7. Lin J, Wu PH, Tarr PT, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004,119:121-35.
8. Tiraby C, and Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol. Metab.2003, 14, 439–441.
9. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
10. Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature .2008,454, 961–967
11. Kajimura S, Seale P, Tomaru T, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes & Dev.2008, 22: 1397–1409.
1.刘志诚,孙凤岷,朱苗花,等.针刺对肥胖大鼠纹状体作用的研究[J ] .针刺研究,2001 ,26 (2) :122 - 126.
2.刘志诚,孙凤岷,朱苗花,等1针刺对肥胖大鼠杏仁核作用的研究[J ]1针刺研究,2000 ,25 (1) :18 - 22.
3.刘志诚,孙凤岷,魏群利,等.针刺对肥胖大鼠中缝核群作用的探讨[J ] .中国中医基础医学杂志,2000 ,6 (7) :52 - 55.
4. Kim SK et al. The association of serum leptin with the reduction of food intake and body weight during electroacupuncture in rats . Pharmacology, Biochemistry and Behavior .2006,83 ,145–149
5. Tian D, Li X, Niu D, et al. Electroacupuncture up-regulated arcuate nucleus alpha-MSH expression in the rat of diet-induced obesity.Beijing Daxue Xuebao. 2003,35:458–61.
6. Lacey JM, Tershakovec AM, Foster GD. Acupuncture for the treatment of obesity: a review of the evidence. Int J Obes Relat Metab Disord .2003,27:419–27.
7. Tian DR, Li XD, Wang F, et al. Up-regulation of the expression of cocaine and amphetamine-regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats.Neurosci Lett .2005,383:17–21.
8. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev. 1984,64 (1): 1-64
9. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
1. Cannon B, Nedergaard J. Brown adipose tissue function and physiological significance. Physiol Rev. 2004,84:277–359
2. Cousin B, Cinti S, Morroni M, et al. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. 1992.J Cell Sci. 103:931–942.
3. Ricquier D, Nechad M, Mory G. Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma. J Clin Endocrinol Metab.1982, 54:803-7.
4. Fukuchi K, Tatsumi M, Ishida Y, et al.Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma. Exp Clin Endocrinol Diabetes.2004, 112:601-3.
5. Nedergaard J, Bengtsson T, and Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab.2007, 293:E444–E452.
6. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009,360:1518-25.
7. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med.2009, 360:1509-17.
8. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men.N Engl J Med. 2009,360:1500-8.
9. Bachman ES, Dhillon H, Zhang CY, et al. Beta AR signaling required for diet-induced thermogenesis and obesity resistance. Science . 2002,297(5582): 843-845.
10. Kralisch S , Klein J, Bluher M, et al. Theraperutic perspectives of adipocytokines. Expert Opin Pharmacother. 2005, 6(6): 863-872.
11. Cinti S. Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ.J Endocrinol Invest.2002, 25(10):823-35.
12. Himms-Hagen J, Melnyk A, Zingaretti MC, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytesl. Am J Physiol CellPhysiol.2000, 279(3):C670-681.
13. Jimenez M, Barbatelli G, Allevi R, et al.β3-Adreno-ceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white fat. Eur J Biochem.2003, 270 (4): 699-705.
14. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
15. Jakus PB, Sandor A, Janaky T, et al.Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation. J. Lipid Res.2008, 49: 332–339.
16. Buckingham M. Myogenic progenitor cells and skeletal myogenesis in vertebrates . Curr Opin Genet Dev. 2006,16(5):525-532.
17. Atit R, Sgaier SK, Mohamed OA, et al. Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse . Dev Biol.2006, 296(1):164-76.
18. Timmons JA, Wennmalm K, Larsson O, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.Proc Natl Acad Sci U S A.2007, 104(11):4401-4406.
19. Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature .2008,454, 961–967
20. Gesta S, Tseng Y H, and Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell .2007,131, 242–256.
21. Hansen JB, Kristiansen K. Regulatory circuits controlling white versus brown adipocyte differentiation. Biochem. J.2006, 398, 153–168.
22. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu. Rev. Cell Dev. Biol.2000, 16, 145–171.
23. Nicholls DG. A history of UCP1. Biochem Soc Trans. 2001,29(Pt 6):751-5.
24. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev.1984,64 (1): 1-64
25. Silva JE, Rabelo R. Regulation of the uncoupling protein gene expression[J]. Eur J Endocrinol.1997, 6:1887.
26. MarxN, Duez H, Fruchart JC, et al. Peroxisome proliferator activated receptors and atherogenesis: regulators of gene expression in vascular cells[ J ]. Circ Res.2004, 94 (9) : 1168 - 1178.
27. Bogacka I, Gettys TW, de Jonge L, et al. The effect of beta-adrenergic and peroxisome proliferator–activated receptor–gamma stimulation on target genes related to lipid metabolism in human subcutaneous adipose tissue. Diabetes Care.2007,30:1179-86.
28. Lin J, Wu PH, Tarr PT, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004,119:121-35.
29. St-Pierre J, Lin J, Krauss S, et al. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells . J. Biol. Chem.2003, 278, 26597–26603.
30. Prpic V, Watson PM, Frampton IC, et al. Adaptive changes in adipocyte gene expression differ in AKR/J and SWR/J mice during diet-induced obesity. J Nutr . 2002,132:3325–32.
31. Louet JF, Hayhurst G, Gonzalez FJ, et al. The coactivator PGC- 1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). J. Biol. Chem. 2002,277: 37991–38000.
32. Tiraby C, and Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol. Metab.2003, 14, 439–441.
33. Nishikata I, Sasaki H, Iga M, et al. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21) -positive AML and blocks G-CSF-induced myeloid differentiation. Blood.2003, 102, 3323–3332.
34. Trievel RC, Beach BM, Dirk LM, et al. Structure and catalytic mechanism of a SET domain protein methyltransferase. Cell.2002, 111: 91–103.
35. Yoshida M, Nosaka K, Yasunaga J, et al.Aberrant expression of the MEL1S geneidentified in association with hypomethylation in adult T-cell leukemia cells . Blood. 2004,103: 2753–2760.
36. Gesta S,Tseng YH, and Kahn CR. Developmental origin of fat: Tracking obesity to its source. Cell.2007, 131: 242–256.
37. Kajimura S, Seale P, Tomaru T, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes & Dev.2008, 22: 1397–1409.
38. Tseng YH, Kokkotou E, Schulz TJ, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure . Nature .2008,454(7207):1000–1004
39. Cerderberg A, Gronning LM, Ahren B, et al. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance[ J ]. Cell, 2001, 106: 563 - 573.
40. Yang X, Smith U. Decreased adipose tissue FOXC2 expression in insulin resistance impaired precursor cell commitment to both white and brown adipose differentiation [ R ]. Diabetes. 2003,52 : A89-A89
41. Yang X, Enerback S, Smith U, et al. Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance [ J ]. Obes Res, 2003, 11 (10) : 1182 - 1191.
42. Pan D, Fujimoto M, Lopes A, et al. Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell.2009, 137(1):73-86.
2. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev. 1984,64 (1): 1-64
3. Lin J, Wu PH, Tarr PT, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004,119:121-35.
4. Tiraby C, and Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol. Metab.2003, 14, 439–441.
5. Cinti S. Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ.J Endocrinol Invest.2002, 25(10):823-35.
6. Himms-Hagen J, Melnyk A, Zingaretti MC, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytesl. Am J Physiol CellPhysiol.2000, 279(3):C670-681.
7. Jimenez M, Barbatelli G, Allevi R, et al.β3-Adreno-ceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white fat. Eur J Biochem.2003, 270 (4): 699-705.
8. Kim DW, Kim BS, et al. Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells. Exp. Mol. Med. Vol. 2003,35(6), 518-526
9. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
10. Nedergaard J, Bengtsson T, and Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab.2007, 293:E444–E452.
11. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men.N Engl J Med. 2009,360:1500-8.
1. Haffner SM, Stern MP, et al. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990; 263: 2893-2898.
2. Levin BE, Hogan S, and Sullivan AC. Initiation and perpetuation of obesity and obesity resistance in rats. Am J Physiol Regulatory Integrative Comp Physiol 256: R766–R771,1989.
3. Tian DR, Li XD, Wang F, et al. Up-regulation of the expression of cocaine and amphetamine-regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats.Neurosci Lett 2005;383:17–21.
4. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009,360:1518-25.
5. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men.N Engl J Med. 2009,360:1500-8.
6. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev. 1984,64 (1): 1-64
7. Lin J, Wu PH, Tarr PT, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004,119:121-35.
8. Tiraby C, and Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol. Metab.2003, 14, 439–441.
9. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
10. Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature .2008,454, 961–967
11. Kajimura S, Seale P, Tomaru T, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes & Dev.2008, 22: 1397–1409.
1.刘志诚,孙凤岷,朱苗花,等.针刺对肥胖大鼠纹状体作用的研究[J ] .针刺研究,2001 ,26 (2) :122 - 126.
2.刘志诚,孙凤岷,朱苗花,等1针刺对肥胖大鼠杏仁核作用的研究[J ]1针刺研究,2000 ,25 (1) :18 - 22.
3.刘志诚,孙凤岷,魏群利,等.针刺对肥胖大鼠中缝核群作用的探讨[J ] .中国中医基础医学杂志,2000 ,6 (7) :52 - 55.
4. Kim SK et al. The association of serum leptin with the reduction of food intake and body weight during electroacupuncture in rats . Pharmacology, Biochemistry and Behavior .2006,83 ,145–149
5. Tian D, Li X, Niu D, et al. Electroacupuncture up-regulated arcuate nucleus alpha-MSH expression in the rat of diet-induced obesity.Beijing Daxue Xuebao. 2003,35:458–61.
6. Lacey JM, Tershakovec AM, Foster GD. Acupuncture for the treatment of obesity: a review of the evidence. Int J Obes Relat Metab Disord .2003,27:419–27.
7. Tian DR, Li XD, Wang F, et al. Up-regulation of the expression of cocaine and amphetamine-regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats.Neurosci Lett .2005,383:17–21.
8. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev. 1984,64 (1): 1-64
9. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
1. Cannon B, Nedergaard J. Brown adipose tissue function and physiological significance. Physiol Rev. 2004,84:277–359
2. Cousin B, Cinti S, Morroni M, et al. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. 1992.J Cell Sci. 103:931–942.
3. Ricquier D, Nechad M, Mory G. Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma. J Clin Endocrinol Metab.1982, 54:803-7.
4. Fukuchi K, Tatsumi M, Ishida Y, et al.Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma. Exp Clin Endocrinol Diabetes.2004, 112:601-3.
5. Nedergaard J, Bengtsson T, and Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab.2007, 293:E444–E452.
6. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009,360:1518-25.
7. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med.2009, 360:1509-17.
8. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men.N Engl J Med. 2009,360:1500-8.
9. Bachman ES, Dhillon H, Zhang CY, et al. Beta AR signaling required for diet-induced thermogenesis and obesity resistance. Science . 2002,297(5582): 843-845.
10. Kralisch S , Klein J, Bluher M, et al. Theraperutic perspectives of adipocytokines. Expert Opin Pharmacother. 2005, 6(6): 863-872.
11. Cinti S. Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ.J Endocrinol Invest.2002, 25(10):823-35.
12. Himms-Hagen J, Melnyk A, Zingaretti MC, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytesl. Am J Physiol CellPhysiol.2000, 279(3):C670-681.
13. Jimenez M, Barbatelli G, Allevi R, et al.β3-Adreno-ceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white fat. Eur J Biochem.2003, 270 (4): 699-705.
14. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab.2007, 6, 38–54.
15. Jakus PB, Sandor A, Janaky T, et al.Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation. J. Lipid Res.2008, 49: 332–339.
16. Buckingham M. Myogenic progenitor cells and skeletal myogenesis in vertebrates . Curr Opin Genet Dev. 2006,16(5):525-532.
17. Atit R, Sgaier SK, Mohamed OA, et al. Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse . Dev Biol.2006, 296(1):164-76.
18. Timmons JA, Wennmalm K, Larsson O, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.Proc Natl Acad Sci U S A.2007, 104(11):4401-4406.
19. Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature .2008,454, 961–967
20. Gesta S, Tseng Y H, and Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell .2007,131, 242–256.
21. Hansen JB, Kristiansen K. Regulatory circuits controlling white versus brown adipocyte differentiation. Biochem. J.2006, 398, 153–168.
22. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu. Rev. Cell Dev. Biol.2000, 16, 145–171.
23. Nicholls DG. A history of UCP1. Biochem Soc Trans. 2001,29(Pt 6):751-5.
24. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physol Rev.1984,64 (1): 1-64
25. Silva JE, Rabelo R. Regulation of the uncoupling protein gene expression[J]. Eur J Endocrinol.1997, 6:1887.
26. MarxN, Duez H, Fruchart JC, et al. Peroxisome proliferator activated receptors and atherogenesis: regulators of gene expression in vascular cells[ J ]. Circ Res.2004, 94 (9) : 1168 - 1178.
27. Bogacka I, Gettys TW, de Jonge L, et al. The effect of beta-adrenergic and peroxisome proliferator–activated receptor–gamma stimulation on target genes related to lipid metabolism in human subcutaneous adipose tissue. Diabetes Care.2007,30:1179-86.
28. Lin J, Wu PH, Tarr PT, et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004,119:121-35.
29. St-Pierre J, Lin J, Krauss S, et al. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells . J. Biol. Chem.2003, 278, 26597–26603.
30. Prpic V, Watson PM, Frampton IC, et al. Adaptive changes in adipocyte gene expression differ in AKR/J and SWR/J mice during diet-induced obesity. J Nutr . 2002,132:3325–32.
31. Louet JF, Hayhurst G, Gonzalez FJ, et al. The coactivator PGC- 1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). J. Biol. Chem. 2002,277: 37991–38000.
32. Tiraby C, and Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol. Metab.2003, 14, 439–441.
33. Nishikata I, Sasaki H, Iga M, et al. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21) -positive AML and blocks G-CSF-induced myeloid differentiation. Blood.2003, 102, 3323–3332.
34. Trievel RC, Beach BM, Dirk LM, et al. Structure and catalytic mechanism of a SET domain protein methyltransferase. Cell.2002, 111: 91–103.
35. Yoshida M, Nosaka K, Yasunaga J, et al.Aberrant expression of the MEL1S geneidentified in association with hypomethylation in adult T-cell leukemia cells . Blood. 2004,103: 2753–2760.
36. Gesta S,Tseng YH, and Kahn CR. Developmental origin of fat: Tracking obesity to its source. Cell.2007, 131: 242–256.
37. Kajimura S, Seale P, Tomaru T, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes & Dev.2008, 22: 1397–1409.
38. Tseng YH, Kokkotou E, Schulz TJ, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure . Nature .2008,454(7207):1000–1004
39. Cerderberg A, Gronning LM, Ahren B, et al. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance[ J ]. Cell, 2001, 106: 563 - 573.
40. Yang X, Smith U. Decreased adipose tissue FOXC2 expression in insulin resistance impaired precursor cell commitment to both white and brown adipose differentiation [ R ]. Diabetes. 2003,52 : A89-A89
41. Yang X, Enerback S, Smith U, et al. Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance [ J ]. Obes Res, 2003, 11 (10) : 1182 - 1191.
42. Pan D, Fujimoto M, Lopes A, et al. Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell.2009, 137(1):73-86.