浏览全部资源
扫码关注微信
白藜芦醇通过激活PKA-PLIN2通路促进HepG2细胞脂滴脂解
Resveratrol improves lipid droplets lipolysis
via up-regulating PKA-PLIN2 pathway in HepG2 cells- 第三军医大学学报 2017年39卷第24期 页码：2345-2351
- 作者机构：
400038 重庆，第三军医大学军事预防医学院营养与食品卫生学教研室，营养与食品安全研究中心，重庆市医学营养研究中心，重庆市营养与食品安全重点实验室
- 作者简介：
[糜漫天，E-mail: mimt@sina.comMI Mantian, E-mail:mimt@sina.com
- 基金信息：国家自然科学基金面上项目(81673154)
DOI：10.16016/j.1000-5404.201709044
中图分类号： R282.71; R285.1; R575.5收稿：2017-09-07，
修回：2017-09-28，
纸质出版：2017-12-30
- 稿件说明：
移动端阅览
叶喜坤, 秦玉, 冉莉, 等. 白藜芦醇通过激活PKA-PLIN2通路促进HepG2细胞脂滴脂解[J]. 第三军医大学学报, 2017,39(24):2345-2351.
Xikun YE, Yu QIN, Li RAN, et al. Resveratrol improves lipid droplets lipolysis
via up-regulating PKA-PLIN2 pathway in HepG2 cells[J]. Journal of Third Military Medical University, 2017, 39(24): 2345-2351.叶喜坤, 秦玉, 冉莉, 等. 白藜芦醇通过激活PKA-PLIN2通路促进HepG2细胞脂滴脂解[J]. 第三军医大学学报, 2017,39(24):2345-2351. DOI： 10.16016/j.1000-5404.201709044.
Xikun YE, Yu QIN, Li RAN, et al. Resveratrol improves lipid droplets lipolysis
via up-regulating PKA-PLIN2 pathway in HepG2 cells[J]. Journal of Third Military Medical University, 2017, 39(24): 2345-2351. DOI： 10.16016/j.1000-5404.201709044.
摘要
目的
2
明确围脂滴蛋白2(perilipinin-2，PLIN2)在白藜芦醇(resveratrol，RSV)改善脂肪变性HepG2细胞脂滴代谢中的作用机制。
方法
2
0.2 mmol/L棕榈酸处理HepG2细胞24 h，建立肝细胞脂肪变性模型。使用0、10、20、40、80 μmol/L RSV及转染PLIN2 siRNA或PKI过表达质粒后，再用40 μmol/L RSV干预24 h，油红O染色检测脂滴形成情况，酶法检测细胞内甘油三酯以及细胞外游离甘油含量，Western blot检测PLIN2蛋白表达，实时定量PCR检测PLIN2 mRNA表达。
结果
2
RSV可以降低脂肪变性HepG2细胞脂滴蓄积程度，促进脂滴的脂解。RSV可以通过促进磷酸化增强PKA的活性，并呈浓度依赖性地上调PLIN2 mRNA和蛋白表达水平(
P
＜0.05)。抑制PKA活性或下调PLIN2表达后，RSV促进脂肪变性HepG2细胞脂解的作用显著减弱(
P
＜0.05)。
结论
2
RSV通过激活PKA-PLIN2通路促进HepG2细胞脂滴脂解过程，从而可能改善非酒精性脂肪性肝病。
Abstract
Objective
2
Elucidate the role of perilipinin-2 (PLIN2) in RSV improving lipid droplet metabolism in liver steatosis in HepG2 cells.
Methods
2
HepG2 cells were incubated with 0.2 mmol/L of palmitic acid (PA) for 24 h to set up a hepatic steatosis model. The cells were then treated with or without a series of concentrations (10
20
40 and 80 μmol/L) of RSV
or transfected with PLIN2 siRNA or PKI overexpression plasmid
40 μmol/L RSV was added for another 24 h. Hepatic lipid accumulation was assayed by Oil Red O staining. Contents of triglyceride in cells and free glycerin glycerol in culture medium were detected by Enzyme method. The protein and mRNA levels of PLIN2 were measured by Western blot assay and real-time quantitative PCR
respectively.
Results
2
RSV reduced the lipid droplet accumulation and increased the lipolysis in PA-induced HepG2 cells. Additionally
RSV increased the activity of PKA by phosphorylation and dose-dependently raised the mRNA and protein levels of PLIN2(
P
<
0.05). The promoting effect of RSV on the lipolysis was significantly reduced by the inhibition of PKA activity and the down-regulation of PLIN2 (
P
<
0.05).
Conclusion
2
RSV promotes lipid droplet lipolysis by activating PKA-PLIN2 pathway in HepG2 cells
and may attenuate non-alcoholic fatty liver disease.
关键词
Keywords
references
GOH V, SILVER D. The lipid droplet as a potential therapeutic target in NAFLD[J]. Semi Liver Dis, 2013, 33(4): 312-320. DOI: 10.1055/s-0033-1358521.
LIBBY A E, BALES E, ORLICKY D J, et al. Perilipin-2 deletion impairs hepatic lipid accumulation by interfering with sterol regulatory element-binding protein (SREBP) activation and altering the hepatic lipidome[J]. J Biol Chem, 2016, 291(46): 24231-24246. DOI: 10.1074/jbc.M116.759795.
CHEN S, ZHAO X, RAN L, et al. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial[J]. Dig Liver Dis, 2015, 47(3): 226-232. DOI: 10.1016/j.dld.2014.11.015.
ZHOU X, CHEN M, ZENG X, et al. Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells[J]. Cell Death Dis, 2014, 5: e1576. DOI: 10.1038/cddis.2014.530.
LIU C, LIAO J Z, LI P Y. Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2017, 23(11): 1964-1973. DOI: 10.3748/wjg.v23.i11.1964.
ZHANG Y, CHEN M L, ZHOU Y, et al. Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway[J]. Mol Nutr Food Res, 2015, 59(8): 1443-1457. DOI: 10.1002/mnfr.201500016.
ZHANG Z C, LIU Y, XIAO L L, et al. Upregulation of miR-125b by estrogen protects against non-alcoholic fatty liver in female mice[J]. J Hepatol, 2015, 63(6): 1466-1475. DOI: 10.1016/j.jhep.2015.07.037.
SINHA R A, FARAH B L, SINGH B K, et al. Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice[J]. Hepatology, 2014, 59(4): 1366-1380.DOI: 10.1002/hep.26667.
ZECHNER R, MADEO F, KRATKY D. Cytosolic lipolysis and lipophagy: two sides of the same coin[J]. Nat Rev Mol Cell Biol, 2017. DOI: 10.1038/nrm.2017.76.
LASA A, SCHWEIGER M, KOTZBECK P, et al. Resveratrol regulates lipolysis via adipose triglyceride lipase[J ] . J Nutr Biochem, 2012, 23(4): 379-384. DOI: 10.1016/j.jnutbio.2010.12.014.
LONDOS C, BRASAEMLE D L, SCHULTZ C J, et al. On the control of lipolysis in adipocytes[J]. Ann N Y Acad Sci, 1999, 892: 155-168.
SZKUDELSKA K, NOGOWSKI L, SZKUDELSKI T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes[J]. J Steroid Biochem Mol Biol, 2009, 113(1-2): 17/24. DOI: 10.1016/j.jsbmb.2008.11.001.
RAYALAM S, DELLA-FERA M A, BAILE C A. Synergism between resveratrol and other phytochemicals: implications for obesity and osteoporosis[J]. Mol Nutr Food Res, 2011, 55(8): 1177-1185. DOI: 10.1002/mnfr.201000616.
HSIAO P J, CHIOU H C, JIANG H J, et al. Pioglitazone enhances cytosolic lipolysis, β-oxidation and autophagy to ameliorate hepatic steatosis[J]. Sci Rep, 2017, 7(1): 9030. DOI: 10.1038/s41598-017-09702-3.
BLUMENSTEIN I, KESERü B, WOLTER F, et al. The chemopreventive agent resveratrol stimulates cyclic AMP-dependent chloride secretion in vitro [J ] . Clin Cancer Res, 2005, 11(15): 5651-5656. DOI:10.1158/1078-0432.CCR-04-2674.
ANDREWS C S, MATSUYAMA S, LEE B C, et al. Resveratrol suppresses NTHi-induced inflammation via up-regulation of the negative regulator MyD88 short[J ] . Sci Rep, 2016, 6: 34445. DOI: 10.1038/srep34445.
CARR R M, AHIMA R S. Pathophysiology of lipid droplet proteins in liver diseases[J]. Exp Cell Res, 2016, 340(2): 187-192. DOI: 10.1016/j.yexcr.2015.10.021.
CONTE M, FRANCESCHI C, SANDRI M, et al. Perilipin 2 and age-related metabolic diseases: a new perspective[J]. Trends Endocrinol Metab, 2016, 27(12): 893-903. DOI: 10.1016/j.tem.2016.09.001.
OKUMURA T. Role of lipid droplet proteins in liver steatosis[J]. J Physiol Biochem, 2011, 67(4): 629-636. DOI: 10.1007/s13105-011-0110-6.
BI J, XIANG Y, CHEN H, et al. Opposite and redundant roles of the two Drosophila perilipins in lipid mobilization[J]. J Cell Sci, 2012, 125(Pt 15): 3568-3577. DOI: 10.1242/jcs.101329.
JIN J X, LEE S, Taweechaipaisankul A, et al. Melatonin regulates lipid metabolism in porcine oocytes[J]. J Pineal Res, 2017, 62(2): e12388. DOI: 10.1111/jpi.12388.
KAUSHIK S, CUERVO A M. AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA[J]. Autophagy, 2016, 12(2): 432-438. DOI: 10.1080/15548627.2015.1124226.
KAUSHIK S, CUERVO A M. Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis[J]. Nat Cell Biol, 2015, 17(6): 759-770. DOI: 10.1038/ncb3166.
MACPHERSON R E, PETERS S J. Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis[J]. Physiol appl, nutr metab, 2015, 40(7): 641-651. DOI: 10.1139/apnm-2014-0485.
0
浏览量
0
下载量
0
CSCD
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
