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:
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.
Resveratrol improves lipid droplets lipolysis via up-regulating PKA-PLIN2 pathway in HepG2 cells
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.
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