Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Protein & Cell

ISSN 1674-800X

ISSN 1674-8018(Online)

CN 11-5886/Q

Postal Subscription Code 80-984

2018 Impact Factor: 7.575

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Protein Cell    2017, Vol. 8 Issue (1) : 4-13    https://doi.org/10.1007/s13238-016-0327-9
REVIEW
Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease
Xuelin Zhang1(),Yang Wang2,Pingsheng Liu2()
1. School of Kinesiology and Health, Capital University of Physical Education and Sports, Beijing 100191, China
2. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
 Download: PDF(499 KB)  
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.
Keywords non-alcoholic fatty liver disease      lipid droplets      genome-wide association study      proteomics      PNPLA3      17β-HSD13     
Corresponding Author(s): Xuelin Zhang,Pingsheng Liu   
Issue Date: 13 February 2017
 Cite this article:   
Xuelin Zhang,Yang Wang,Pingsheng Liu. Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease[J]. Protein Cell, 2017, 8(1): 4-13.
 URL:  
https://academic.hep.com.cn/pac/EN/10.1007/s13238-016-0327-9
https://academic.hep.com.cn/pac/EN/Y2017/V8/I1/4
44 Kotronen A, Johansson LE, Johansson LM, Roos C, Westerbacka J, Hamsten A, Bergholm R, Arkkila P, Arola J, Kiviluoto T, Fisher RM, Ehrenborg E, Orho-Melander M, Ridderstrale M, Groop L, Yki-Jarvinen H (2009) A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 52:1056–1060
https://doi.org/10.1007/s00125-009-1285-z
45 Krahmer N, Farese RV Jr. (2013) Balancing the fat: lipid droplets and human disease. EMBO Mol Med 5:905–915
https://doi.org/10.1002/emmm.201100671
46 Kumari M, Schoiswohl G, Chitraju C, Paar M, Cornaciu I, Rangrez AY, Wongsiriroj N, Nagy HM, Ivanova PT, Scott SA, Knittelfelder O, Rechberger GN, Birner-Gruenberger R, Eder S, Brown HA, Haemmerle G, Oberer M, Lass A, Kershaw EE, Zimmermann R, Zechner R (2012) Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab 15:691–702
https://doi.org/10.1016/j.cmet.2012.04.008
47 Labrie F (2015) All sex steroids are made intracellularly in peripheral tissues by the mechanisms of intracrinology after menopause. J Steroid Biochem Mol Biol 145:133–138
https://doi.org/10.1016/j.jsbmb.2014.06.001
48 Labrie F, Luu-The V, Lin SX, Simard J, Labrie C, El-Alfy M, Pelletier G, Belanger A (2000) Intracrinology: role of the family of 17 betahydroxysteroid dehydrogenases in human physiology and disease. J Mol Endocrinol 25:1–16
https://doi.org/10.1677/jme.0.0250001
49 Ladaru A, Balanescu P, Stan M, Codreanu I, Anca IA (2016) Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review. Biomarkers 21:102–114
https://doi.org/10.3109/1354750X.2015.1118542
50 Li JZ, Ye J, Xue B, Qi J, Zhang J, Zhou Z, Li Q, Wen Z, Li P (2007) Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation. Diabetes 56:2523–2532
https://doi.org/10.2337/db07-0040
51 Li JZ, Huang Y, Karaman R, Ivanova PT, Brown HA, Roddy T, Castro-Perez J, Cohen JC, Hobbs HH (2012) Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest 122:4130–4144
https://doi.org/10.1172/JCI65179
52 Lim JW, Dillon J, Miller M (2014) Proteomic and genomic studies of non-alcoholic fatty liver disease–clues in the pathogenesis. World J Gastroenterol 20:8325–8340
https://doi.org/10.3748/wjg.v20.i26.8325
53 Lin HY, Yu IC, Wang RS, Chen YT, Liu NC, Altuwaijri S, Hsu CL, Ma WL, Jokinen J, Sparks JD, Yeh S, Chang C (2008) Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology 47:1924–1935
https://doi.org/10.1002/hep.22252
54 Liu S, Huang C, Li D, Ren W, Zhang H, Qi M, Li X, Yu L (2007) Molecular cloning and expression analysis of a new gene for short-chain dehydrogenase/reductase 9. Acta Biochim Pol 54:213–218
55 Luu-The V, Labrie F (2010) The intracrine sex steroid biosynthesis pathways. Prog Brain Res 181:177–192
https://doi.org/10.1016/S0079-6123(08)81010-2
1 Anstee QM, Day CP (2013) The genetics of NAFLD. Nat Rev Gastroenterol Hepatol 10:645–655
https://doi.org/10.1038/nrgastro.2013.182
2 Anstee QM, Targher G, Day CP (2013) Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10:330–344
https://doi.org/10.1038/nrgastro.2013.41
56 Ma WL, Lai HC, Yeh S, Cai X, Chang C (2014) Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis. Endocr Relat Cancer 21:R165–R182
https://doi.org/10.1530/ERC-13-0283
57 Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363:166–176
https://doi.org/10.1056/NEJMra0905980
58 Marchais-Oberwinkler S, Henn C, Moller G, Klein T, Negri M, Oster A, Spadaro A, Werth R, Wetzel M, Xu K, Frotscher M, Hartmann RW, Adamski J (2011) 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development. J Steroid Biochem Mol Biol 125:66–82
https://doi.org/10.1016/j.jsbmb.2010.12.013
59 Martin S, Parton RG (2006) Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol 7:373–378
https://doi.org/10.1038/nrm1912
60 McNamara KM, Sasano H (2015) The intracrinology of breast cancer. J Steroid Biochem Mol Biol 145:172–178
https://doi.org/10.1016/j.jsbmb.2014.04.004
61 Michelotti GA, Machado MV, Diehl AM (2013) NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol 10:656–665
https://doi.org/10.1038/nrgastro.2013.183
62 Moeller G, Adamski J (2006) Multifunctionality of human 17betahydroxysteroid dehydrogenases. Mol Cell Endocrinol 248:47–55
https://doi.org/10.1016/j.mce.2005.11.031
63 Moeller G, Adamski J (2009) Integrated view on 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 301:7–19
https://doi.org/10.1016/j.mce.2008.10.040
64 Mostaghel EA (2013) Steroid hormone synthetic pathways in prostate cancer. Transl Androl Urol 2:212–227
65 Murphy DJ (2001) The biogenesis and functions of lipid bodies in animals, plants and microorganisms. Prog Lipid Res 40:325–438
https://doi.org/10.1016/S0163-7827(01)00013-3
66 Musso G, Cassader M, Rosina F, Gambino R (2012) Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 55:885–904
https://doi.org/10.1007/s00125-011-2446-4
67 Pirazzi C, Adiels M, Burza MA, Mancina RM, Levin M, Stahlman M, Taskinen MR, Orho-Melander M, Perman J, Pujia A, Andersson L, Maglio C, Montalcini T, Wiklund O, Boren J, Romeo S (2012) Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro. J Hepatol 57:1276–1282
https://doi.org/10.1016/j.jhep.2012.07.030
68 Pirazzi C, Valenti L, Motta BM, Pingitore P, Hedfalk K, Mancina RM, Burza MA, Indiveri C, Ferro Y, Montalcini T, Maglio C, Dongiovanni P, Fargion S, Rametta R, Pujia A, Andersson L, Ghosal S, Levin M, Wiklund O, Iacovino M, Boren J, Romeo S (2014) PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum Mol Genet 23:4077–4085
https://doi.org/10.1093/hmg/ddu121
69 Rinella M, Charlton M (2016) The globalization of non-alcoholic fatty liver disease-prevalence and impact on world health. Hepatology 64(1):19–22
https://doi.org/10.1002/hep.28524
70 Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH (2008) Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40:1461–1465
https://doi.org/10.1038/ng.257
71 Ronchetti A, Prati D, Pezzotta MG, Tavian D, Colombo R, Callea F, Colli A (2008) Severe steatohepatitis in a patient with a rare neutral lipid storage disorder due to ABHD5 mutation. J Hepatol 49:474–477
https://doi.org/10.1016/j.jhep.2008.05.027
72 Rotinen M, Villar J, Celay J, Encio I (2010) Type 10 17betahydroxysteroid dehydrogenase expression is regulated by C/EBPbeta in HepG2 cells. J Steroid Biochem Mol Biol 122:164–171
https://doi.org/10.1016/j.jsbmb.2010.07.003
73 Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ, Nash CRN (2010) The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology 52:894–903
https://doi.org/10.1002/hep.23759
74 Schwingel PA, Zoppi CC, Cotrim HP (2011) Increased liver steatosis in anabolic-androgenic steroid users: more evidence towards toxicant-associated fatty liver disease development. Liver Int 31:1240–1241
https://doi.org/10.1111/j.1478-3231.2011.02552.x
75 Shen M, Shi H (2015) Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis. Int J Endocrinol 2015:294278
https://doi.org/10.1155/2015/294278
76 Smagris E, BasuRay S, Li J, Huang Y, Lai KM, Gromada J, Cohen JC, Hobbs HH (2015) Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis. Hepatology 61:108–118
https://doi.org/10.1002/hep.27242
77 Smith BW, Adams LA (2011) Non-alcoholic fatty liver disease. Crit Rev Clin Lab Sci 48:97–113
https://doi.org/10.3109/10408363.2011.596521
78 Sookoian S, Pirola CJ (2015) Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol 21:711–725
https://doi.org/10.3748/wjg.v21.i3.711
79 Sookoian S, Castano GO, Burgueno AL, Gianotti TF, Rosselli MS, Pirola CJ (2009) A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res 50:2111–2116
https://doi.org/10.1194/jlr.P900013-JLR200
80 Speliotes EK, Butler JL, Palmer CD, Voight BF, Consortium G, Consortium MI, Nash CNR, Hirschhorn JN (2010) PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 52:904–912
https://doi.org/10.1002/hep.23768
81 Srinivasan R, Hadzic N, Fischer J, Knisely AS (2004) Steatohepatitis and unsuspected micronodular cirrhosis in Dorfman-Chanarin syndrome with documented ABHD5 mutation. J Pediatr 144:662–665
https://doi.org/10.1016/j.jpeds.2004.01.036
82 Straub BK, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P (2008) Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology 47:1936–1946
https://doi.org/10.1002/hep.22268
83 Su W, Wang Y, Jia X, Wu W, Li L, Tian X, Li S, Wang C, Xu H, Cao J, Han Q, Xu S, Chen Y, Zhong Y, Zhang X, Liu P, Gustafsson JA, Guan Y (2014) Comparative proteomic study reveals 17beta-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease. Proc Natl Acad Sci USA 111:11437–11442
https://doi.org/10.1073/pnas.1410741111
84 Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363:1341–1350
https://doi.org/10.1056/NEJMra0912063
85 Tauchi-Sato K, Ozeki S, Houjou T, Taguchi R, Fujimoto T (2002) The surface of lipid droplets is a phospholipid monolayer with a unique Fatty Acid composition. J Biol Chem 277:44507–44512
https://doi.org/10.1074/jbc.M207712200
86 Varlamov O, Bethea CL, Roberts CT Jr. (2014) Sex-specific differences in lipid and glucose metabolism. Front Endocrinol (Lausanne) 5:241
87 Volzke H, Aumann N, Krebs A, Nauck M, Steveling A, Lerch MM, Rosskopf D, Wallaschofski H (2010) Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men. Int J Androl 33:45–53
https://doi.org/10.1111/j.1365-2605.2009.00953.x
88 Wang FS, Fan JG, Zhang Z, Gao B, Wang HY (2014) The global burden of liver disease: the major impact of China. Hepatology 60:2099–2108
https://doi.org/10.1002/hep.27406
89 Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P, Zhang X, Gu Y, Xu Y, Wang Z, Li Z, Zhang H, Ye J (2015) Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis. Hepatology 61:870–882
https://doi.org/10.1002/hep.27409
90 Yang L, Ding Y, Chen Y, Zhang S, Huo C, Wang Y, Yu J, Zhang P, Na H, Zhang H, Ma Y, Liu P (2012) The proteomics of lipid droplets: structure, dynamics, and functions of the organelle conserved from bacteria to humans. J Lipid Res 53:1245–1253
https://doi.org/10.1194/jlr.R024117
91 Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M (2015) Global epidemiology of non-alcoholic fatty liver diseasemeta-analytic assessment of prevalence, incidence and outcomes. Hepatology 64(1):73–84
https://doi.org/10.1002/hep.28431
92 Zehmer JK, Huang Y, Peng G, Pu J, Anderson RG, Liu P (2009) A role for lipid droplets in inter-membrane lipid traffic. Proteomics 9:914–921
https://doi.org/10.1002/pmic.200800584
3 Aragno M, Tomasinelli CE, Vercellinatto I, Catalano MG, Collino M, Fantozzi R, Danni O, Boccuzzi G (2009) SREBP-1c in nonalcoholic fatty liver disease induced by Western-type high-fat diet plus fructose in rats. Free Radic Biol Med 47:1067–1074
https://doi.org/10.1016/j.freeradbiomed.2009.07.016
4 Awai HI, Yu EL, Ellis LS, Schwimmer JB (2014) Liver toxicity of anabolic androgenic steroid use in an adolescent with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 59:e32–e33
https://doi.org/10.1097/mpg.0b013e3182952e74
5 Barros RP, Gustafsson JA (2011) Estrogen receptors and the metabolic network. Cell Metab 14:289–299
https://doi.org/10.1016/j.cmet.2011.08.005
6 Basantani MK, Sitnick MT, Cai L, Brenner DS, Gardner NP, Li JZ, Schoiswohl G, Yang K, Kumari M, Gross RW, Zechner R, Kershaw EE (2011) Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J Lipid Res 52:318–329
https://doi.org/10.1194/jlr.M011205
7 Blaner WS, O’Byrne SM, Wongsiriroj N, Kluwe J, D’Ambrosio DM, Jiang H, Schwabe RF, Hillman EM, Piantedosi R, Libien J (2009) Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage. Biochim Biophys Acta 1791:467–473
https://doi.org/10.1016/j.bbalip.2008.11.001
8 Brady CW (2015) Liver disease in menopause. World J Gastroenterol 21:7613–7620
https://doi.org/10.3748/wjg.v21.i25.7613
9 Brzozowska MM, Ostapowicz G, Weltman MD (2009) An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome. J Gastroenterol Hepatol 24:243–247
https://doi.org/10.1111/j.1440-1746.2008.05740.x
10 Carr RM, Ahima RS (2016) Pathophysiology of lipid droplet proteins in liver diseases. Exp Cell Res 340:187–192
https://doi.org/10.1016/j.yexcr.2015.10.021
11 Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Coin LJ, Deng G, Gieger C, Heard-Costa NL, Hottenga JJ, Kuhnel B, Kumar V, Lagou V, Liang L, Luan J, Vidal PM, Mateo Leach I, O’Reilly PF, Peden JF, Rahmioglu N, Soininen P, Speliotes EK, Yuan X, Thorleifsson G, Alizadeh BZ, Atwood LD, Borecki IB, Brown MJ, Charoen P, Cucca F, Das D, de Geus EJ, Dixon AL, Doring A, Ehret G, Eyjolfsson GI, Farrall M, Forouhi NG, Friedrich N, Goessling W, Gudbjartsson DF, Harris TB, Hartikainen AL, Heath S, Hirschfield GM, Hofman A, Homuth G, Hypponen E, Janssen HL, Johnson T, Kangas AJ, Kema IP, Kuhn JP, Lai S, Lathrop M, Lerch MM, Li Y, Liang TJ, Lin JP, Loos RJ, Martin NG, Moffatt MF, Montgomery GW, Munroe PB, Musunuru K, Nakamura Y, O’Donnell CJ, Olafsson I, Penninx BW, Pouta A, Prins BP, Prokopenko I, Puls R, Ruokonen A, Savolainen MJ, Schlessinger D, Schouten JN, Seedorf U, Sen-Chowdhry S, Siminovitch KA, Smit JH, Spector TD, Tan W, Teslovich TM, Tukiainen T, Uitterlinden AG, Van der Klauw MM, Vasan RS, Wallace C, Wallaschofski H, Wichmann HE, Willemsen G, Wurtz P, Xu C, Yerges-Armstrong LM, Alcohol Genome-wide Association C, Diabetes Genetics R, Meta-analyses S, Genetic Investigation of Anthropometric Traits C, Global Lipids Genetics C, Genetics of Liver Disease C, International Consortium for Blood P, Meta-analyses of G, Insulin-Related Traits C, Abecasis GR, Ahmadi KR, Boomsma DI, Caulfield M, Cookson WO, van Duijn CM, Froguel P, Matsuda K, McCarthy MI, Meisinger C, Mooser V, Pietilainen KH, Schumann G, Snieder H, Sternberg MJ, Stolk RP, Thomas HC, Thorsteinsdottir U, Uda M, Waeber G, Wareham NJ, Waterworth DM, Watkins H, Whitfield JB, Witteman JC, Wolffenbuttel BH, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Volzke H, Schadt EE, Scott J, Jarvelin MR, Elliott P, Kooner JS (2011) Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet 43:1131–1138
https://doi.org/10.1038/ng.970
12 Charlton M, Angulo P, Chalasani N, Merriman R, Viker K, Charatcharoenwitthaya P, Sanderson S, Gawrieh S, Krishnan A, Lindor K (2008) Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology 47:484–492
https://doi.org/10.1002/hep.22063
13 Chen W, Chang B, Li L, Chan L (2010) Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology 52:1134–1142
https://doi.org/10.1002/hep.23812
14 Cohen JC, Horton JD, Hobbs HH (2011) Human fatty liver disease: old questions and new insights. Science 332:1519–1523
https://doi.org/10.1126/science.1204265
15 Cole LK, Jacobs RL, Vance DE (2010) Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology 52:1258–1265
https://doi.org/10.1002/hep.23813
16 Crunk AE, Monks J, Murakami A, Jackman M, Maclean PS, Ladinsky M, Bales ES, Cain S, Orlicky DJ, McManaman JL (2013) Dynamic regulation of hepatic lipid droplet properties by diet. PLoS One 8:e67631
https://doi.org/10.1371/journal.pone.0067631
17 Ding ZY, Jin GN, Liang HF, Wang W, Chen WX, Datta PK, Zhang MZ, Zhang B, Chen XP (2013) Transforming growth factor beta induces expression of connective tissue growth factor in hepatic progenitor cells through Smad independent signaling. Cell Signal 25:1981–1992
https://doi.org/10.1016/j.cellsig.2013.05.027
18 DiStefano MT, Danai LV, Roth Flach RJ, Chawla A, Pedersen DJ, Guilherme A, Czech MP (2015) The lipid droplet protein hypoxiainducible gene 2 promotes hepatic triglyceride deposition by inhibiting lipolysis. J Biol Chem 290:15175–15184
https://doi.org/10.1074/jbc.M115.650184
19 Donati B, Motta BM, Pingitore P, Meroni M, Pietrelli A, Alisi A, Petta S, Xing C, Dongiovanni P, Del Menico B, Rametta R, Mancina RM, Badiali S, Fracanzani AL, Craxi A, Fargion S, Nobili V, Romeo S, Valenti L (2016) The rs2294918 E434K variant modulates patatin-like phospholipase domain-containing 3 expression and liver damage. Hepatology 63:787–798
https://doi.org/10.1002/hep.28370
20 Dongiovanni P, Donati B, Fares R, Lombardi R, Mancina RM, Romeo S, Valenti L (2013) PNPLA3 I148M polymorphism and progressive liver disease. World J Gastroenterol 19:6969–6978
https://doi.org/10.3748/wjg.v19.i41.6969
21 Dowman JK, Armstrong MJ, Tomlinson JW, Newsome PN (2011) Current therapeutic strategies in non-alcoholic fatty liver disease. Diabetes Obes Metab 13:692–702
https://doi.org/10.1111/j.1463-1326.2011.01403.x
22 Fujii H, Ikura Y, Arimoto J, Sugioka K, Iezzoni JC, Park SH, Naruko T, Itabe H, Kawada N, Caldwell SH, Ueda M (2009) Expression of perilipin and adipophilin in nonalcoholic fatty liver disease; relevance to oxidative injury and hepatocyte ballooning. J Atheroscler Thromb 16:893–901
https://doi.org/10.5551/jat.2055
23 Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A (2013) Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5:1544–1560
https://doi.org/10.3390/nu5051544
24 Greenberg AS, Coleman RA, Kraemer FB, McManaman JL, Obin MS, Puri V, Yan QW, Miyoshi H, Mashek DG (2011) The role of lipid droplets in metabolic disease in rodents and humans. J Clin Invest 121:2102–2110
https://doi.org/10.1172/JCI46069
25 Gregorich ZR, Ge Y (2014) Top-down proteomics in health and disease: challenges and opportunities. Proteomics 14:1195–1210
https://doi.org/10.1002/pmic.201300432
26 Gressner OA, Lahme B, Siluschek M, Rehbein K, Herrmann J, Weiskirchen R, Gressner AM (2008) Activation of TGF-beta within cultured hepatocytes and in liver injury leads to intracrine signaling with expression of connective tissue growth factor. J Cell Mol Med 12:2717–2730
https://doi.org/10.1111/j.1582-4934.2008.00260.x
27 Guo F, Ma Y, Kadegowda AK, Betters JL, Xie P, Liu G, Liu X, Miao H, Ou J, Su X, Zheng Z, Xue B, Shi H, Yu L (2013) Deficiency of liver comparative gene identification-58 causes steatohepatitis and fibrosis in mice. J Lipid Res 54:2109–2120
https://doi.org/10.1194/jlr.M035519
28 Hall AM, Brunt EM, Chen Z, Viswakarma N, Reddy JK, Wolins NE, Finck BN (2010) Dynamic and differential regulation of proteins that coat lipid droplets in fatty liver dystrophic mice. J Lipid Res 51:554–563
https://doi.org/10.1194/jlr.M000976
29 Hanash S (2003) Disease proteomics. Nature 422:226–232
https://doi.org/10.1038/nature01514
30 Hardy J, Singleton A (2009) Genomewide association studies and human disease. N Engl J Med 360:1759–1768
https://doi.org/10.1056/NEJMra0808700
31 Hardy T, Oakley F, Anstee QM, Day CP (2016) Nonalcoholic fatty liver disease: pathogenesis and disease spectrum. Annu Rev Pathol 11:451–496
https://doi.org/10.1146/annurev-pathol-012615-044224
32 Hashimoto E, Tokushige K (2011) Prevalence, gender, ethnic variations, and prognosis of NASH. J Gastroenterol 46(Suppl1):63–69
https://doi.org/10.1007/s00535-010-0311-8
33 He S, McPhaul C, Li JZ, Garuti R, Kinch L, Grishin NV, Cohen JC, Hobbs HH (2010) A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem 285:6706–6715
https://doi.org/10.1074/jbc.M109.064501
34 Hoekstra M, Li Z, Kruijt JK, Van Eck M, Van Berkel TJ, Kuiper J (2010) The expression level of non-alcoholic fatty liver diseaserelated gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status. J Hepatol 52:244–251
https://doi.org/10.1016/j.jhep.2009.11.004
35 Horiguchi Y, Araki M, Motojima K (2008) 17beta-Hydroxysteroid dehydrogenase type 13 is a liver-specific lipid droplet-associated protein. Biochem Biophys Res Commun 370:235–238
https://doi.org/10.1016/j.bbrc.2008.03.063
36 Huang Y, He S, Li JZ, Seo YK, Osborne TF, Cohen JC, Hobbs HH (2010) A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci USA 107:7892–7897
https://doi.org/10.1073/pnas.1003585107
37 Huang Y, Cohen JC, Hobbs HH (2011) Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease. J Biol Chem 286:37085–37093
https://doi.org/10.1074/jbc.M111.290114
38 Kampf C, Mardinoglu A, Fagerberg L, Hallstrom BM, Edlund K, Lundberg E, Ponten F, Nielsen J, Uhlen M (2014) The human liver-specific proteome defined by transcriptomics and antibodybased profiling. FASEB J 28:2901–2914
https://doi.org/10.1096/fj.14-250555
39 Kelley CE, Brown AJ, Diehl AM, Setji TL (2014) Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol 20:14172–14184
https://doi.org/10.3748/wjg.v20.i39.14172
40 Khan SA, Wollaston-Hayden EE, Markowski TW, Higgins L, Mashek DG (2015) Quantitative analysis of the murine lipid dropletassociated proteome during diet-induced hepatic steatosis. J Lipid Res 56:2260–2272
https://doi.org/10.1194/jlr.M056812
41 Kim S, Kwon H, Park JH, Cho B, Kim D, Oh SW, Lee CM, Choi HC (2012) A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease. BMC Gastroenterol 12:69
https://doi.org/10.1186/1471-230X-12-69
42 Kimmel AR, Brasaemle DL, McAndrews-Hill M, Sztalryd C, Londos C (2010) Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J Lipid Res 51:468–471
https://doi.org/10.1194/jlr.R000034
43 Kollerits B, Coassin S, Kiechl S, Hunt SC, Paulweber B, Willeit J, Brandstatter A, Lamina C, Adams TD, Kronenberg F (2010) A common variant in the adiponutrin gene influences liver enzyme values. J Med Genet 47:116–119
https://doi.org/10.1136/jmg.2009.066597
[1] Xu Zhang, Xuetao Ji, Qian Wang, John Zhong Li. New insight into inter-organ crosstalk contributing to the pathogenesis of nonalcoholic fatty liver disease (NAFLD)[J]. Protein Cell, 2018, 9(2): 164-177.
[2] Xiaowen Zheng, Feng Chen, Qian Zhang, Yulan Liu, Peng You, Shan Sun, Jiuxiang Lin, Ning Chen. Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease[J]. Protein Cell, 2017, 8(9): 686-695.
[3] Yong Zeng,Fei-Yan Deng,Wei Zhu,Lan Zhang,Hao He,Chao Xu,Qing Tian,Ji-Gang Zhang,Li-Shu Zhang,Hong-Gang Hu,Hong-Wen Deng. Mass spectrometry based proteomics profiling of human monocytes[J]. Protein Cell, 2017, 8(2): 123-133.
[4] Yufei Yang,Mo Hu,Kaiwen Yu,Xiangmei Zeng,Xiaoyun Liu. Mass spectrometry-based proteomic approaches to study pathogenic bacteria-host interactions[J]. Protein Cell, 2015, 6(4): 265-274.
[5] Linlin Zhang,Shanshan Liu,Ningning Liu,Yong Zhang,Min Liu,Dengwen Li,Edward Seto,Tso-Pang Yao,Wenqing Shui,Jun Zhou. Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity[J]. Protein Cell, 2015, 6(1): 42-54.
[6] Jiawen Wang,Dongyuan Lü,Debin Mao,Mian Long. Mechanomics: an emerging field between biology and biomechanics[J]. Protein Cell, 2014, 5(7): 518-531.
[7] Rui Chen, Shancheng Ren, Yinghao Sun. Genome-wide association studies on prostate cancer: the end or the beginning?[J]. Prot Cell, 2013, 4(9): 677-686.
[8] Xiulan Chen, Shasha Wei, Fuquan Yang. Mitochondria in the pathogenesis of diabetes: a proteomic view[J]. Prot Cell, 2012, 3(9): 648-660.
[9] Peter Roepstorff. Mass spectrometry based proteomics, background, status and future needs[J]. Prot Cell, 2012, 3(9): 641-647.
[10] Zhi-Ping Liu, Luonan Chen. Proteome-wide prediction of protein-protein interactions from high-throughput data[J]. Prot Cell, 2012, 3(7): 508-520.
[11] Shirly O. T. Curreem, Rory M. Watt, Susanna K. P. Lau, Patrick C. Y. Woo. Two-dimensional gel electrophoresis in bacterial proteomics[J]. Prot Cell, 2012, 3(5): 346-363.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed