Pathophysiology of lipid droplet proteins in liver diseases

Experimental Cell Research

Volumn 340, Issue 2, 2016, Pages 187-192

  Carr, Rotonya M ^a   Ahima, Rexford S ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Alcohol; Diabetes; HCV; Hepatitis; Lipid droplet; Lipids; Liver; NAFLD; Obesity; Perilipin; Steatosis

Indexed keywords

FAT DROPLET; HYPOXIA INDUCIBLE PROTEIN 2; LIPID DROPLET PROTEIN; PERILIPIN; PERILIPIN 1; PERILIPIN 2; PERILIPIN 4; PERILIPIN 5; PHOSPHOLIPASE DOMAIN CONTAINING 3; PROTEIN DERIVATIVE; UNCLASSIFIED DRUG; LIPID; TRIACYLGLYCEROL;

ALCOHOL LIVER DISEASE; HEPATITIS C; HUMAN; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; REVIEW; ANIMAL; LIPID METABOLISM; LIVER; LIVER CELL; METABOLISM; PHYSIOLOGY;

ANIMALS; HEPATOCYTES; HUMANS; LIPID DROPLETS; LIPID METABOLISM; LIPIDS; LIVER; TRIGLYCERIDES;

EID: 84957949209     PISSN: 00144827     EISSN: 10902422     Source Type: Journal    
DOI: 10.1016/j.yexcr.2015.10.021     Document Type: Review

References (62)

1. Brasaemle D.L., Wolins N.E. Packaging of fat: an evolving model of lipid droplet assembly and expansion. J. Biol. Chem.. 2012, 287:2273-2279.
2. Ploegh H.L. A lipid-based model for the creation of an escape hatch from the endoplasmic reticulum. Nature. 2007, 448:435-438.
3. Walther T.C., Farese R.V. The life of lipid droplets. Biochim. Biophys. Acta 2009, 1791:459-466.
4. Gimm T., Wiese M., Teschemacher B., Deggerich A., Schodel J., Knaup K.X., Hackenbeck T., Hellerbrand C., Amann K., Wiesener M.S., Honing S., Eckardt K.U., Warnecke C. Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. FASEB J. 2010, 24:4443-4458.
5. Inohara N., Koseki T., Chen S., Wu X., Nunez G. Cide, a novel family of cell death activators with homology to the 45 kda subunit of the DNA fragmentation factor. EOMB J. 1998, 17:2526-2533.
6. Ruhanen H., Perttila J., Holtta-Vuori M., Zhou Y., Yki-Jarvinen H., Ikonen E., Kakela R., Olkkonen V.M. Pnpla3 mediates hepatocyte triacylglycerol remodeling. J. Lipid Res. 2014, 55:739-746.
7. Jenkins C.M., Mancuso D.J., Yan W., Sims H.F., Gibson B., Gross R.W. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase a2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J. Biol. Chem.. 2004, 279:48968-48975.
8. Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in pnpla3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet.. 2008, 40:1461-1465.
9. Mashek D.G., Khan S.A., Sathyanarayan A., Ploeger J.M., Franklin M.P. Hepatic lipid droplet biology: Getting to the root of fatty liver. Hepatology. 2015.
10. Messina J.P., Humphreys I., Flaxman A., Brown A., Cooke G.S., Pybus O.G., Barnes E. Global distribution and prevalence of hepatitis c virus genotypes. Hepatology. 2015, 61:77-87.
11. Scheel T.K., Rice C.M. Understanding the hepatitis c virus life cycle paves the way for highly effective therapies. Nat. Med. 2013, 19:837-849.
12. Herker E., Harris C., Hernandez C., Carpentier A., Kaehlcke K., Rosenberg A.R., Farese R.V., Ott M. Efficient hepatitis c virus particle formation requires diacylglycerol acyltransferase-1. Nat. Med. 2010, 16:1295-1298.
13. Tanaka T., Kuroda K., Ikeda M., Wakita T., Kato N., Makishima M. Hepatitis c virus ns4b targets lipid droplets through hydrophobic residues in the amphipathic helices. J. Lipid Res.. 2013, 54:881-892.
14. Camus G., Herker E., Modi A.A., Haas J.T., Ramage H.R., Farese R.V., Ott M. Diacylglycerol acyltransferase-localizes hepatitis c virus ns5a protein to lipid droplets and enhances ns5a interaction with the viral capsid core. J. Biol. Chem.. 2013, 288:9915-9923.
15. Salloum S., Wang H., Ferguson C., Parton R.G., Tai A.W. Rab18 binds to hepatitis c virus ns5a and promotes interaction between sites of viral replication and lipid droplets. PLoS Pathog. 2013, 9:e1003513.
16. Vogt D.A., Camus G., Herker E., Webster B.R., Tsou C.L., Greene W.C., Yen T.S., Ott M. Lipid droplet-binding protein tip47 regulates hepatitis c virus rna replication through interaction with the viral ns5a protein. PLoS Pathog. 2013, 9:e1003302.
17. Straub B.K., Stoeffel P., Heid H., Zimbelmann R., Schirmacher P. Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology. 2008, 47:1936-1946.
18. Wu X., Lee E.M., Hammack C., Robotham J.M., Basu M., Lang J., Brinton M.A., Tang H. Cell death-inducing dffa-like effector b is required for hepatitis c virus entry into hepatocytes. J. Virol. 2014, 88:8433-8444.
19. Hagist S., Sultmann H., Millonig G., Hebling U., Kieslich D., Kuner R., Balaguer S., Seitz H.K., Poustka A., Mueller S. In vitro-targeted gene identification in patients with hepatitis c using a genome-wide microarray technology. Hepatology. 2009, 49:378-386.
20. Trepo E., Pradat P., Potthoff A., Momozawa Y., Quertinmont E., Gustot T., Lemmers A., Berthillon P., Amininejad L., Chevallier M., Schlue J., Kreipe H., Deviere J., Manns M., Trepo C., Sninsky J., Wedemeyer H., Franchimont D., Moreno C. Impact of patatin-like phospholipase-(rs738409 c>g) polymorphism on fibrosis progression and steatosis in chronic hepatitis c. Hepatology. 2011, 54:60-69.
21. Adinolfi L.E., Gambardella M., Andreana A., Tripodi M.F., Utili R., Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis c patients and correlates with specific hcv genotype and visceral obesity. Hepatology. 2001, 33:1358-1364.
22. Chalasani N., Younossi Z., Lavine J.E., Diehl A.M., Brunt E.M., Cusi K., Charlton M., Sanyal A.J. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the american association for the study of liver diseases, american college of gastroenterology, and the american gastroenterological association. Hepatology. 2012, 55:2005-2023.
23. Benhamed F., Denechaud P.D., Lemoine M., Robichon C., Moldes M., Bertrand-Michel J., Ratziu V., Serfaty L., Housset C., Capeau J., Girard J., Guillou H., Postic C. The lipogenic transcription factor chrebp dissociates hepatic steatosis from insulin resistance in mice and humans. J. Clin. Investig. 2012, 122:2176-2194.
24. Dentin R., Benhamed F., Hainault I., Fauveau V., Foufelle F., Dyck J.R., Girard J., Postic C. Liver-specific inhibition of chrebp improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes. 2006, 55:2159-2170.
25. Yahagi N., Shimano H., Hasty A.H., Matsuzaka T., Ide T., Yoshikawa T., Amemiya-Kudo M., Tomita S., Okazaki H., Tamura Y., Iizuka Y., Ohashi K., Osuga J., Harada K., Gotoda T., Nagai R., Ishibashi S., Yamada N. Absence of sterol regulatory element-binding protein-(srebp-1) ameliorates fatty livers but not obesity or insulin resistance in lep(ob)/lep(ob) mice. J. Biol. Chem.. 2002, 277:19353-19357.
26. Caldwell S.H., Swerdlow R.H., Khan E.M., Iezzoni J.C., Hespenheide E.E., Parks J.K., Parker W.D. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J. Hepatol.. 1999, 31:430-434.
27. Vedala A., Wang W., Neese R.A., Christiansen M.P., Hellerstein M.K. Delayed secretory pathway contributions to vldl-triglycerides from plasma nefa, diet, and de novo lipogenesis in humans. J. Lipid Res.. 2006, 47:2562-2574.
28. Lambert J.E., Ramos-Roman M.A., Browning J.D., Parks E.J. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014, 146:726-735.
29. Varela G.M., Antwi D.A., Dhir R., Yin X., Singhal N.S., Graham M.J., Crooke R.M., Ahima R.S. Inhibition of adrp prevents diet-induced insulin resistance. Am. J. Physiol. Gastrointest. Liver Physiol.. 2008, 295:G621-628.
30. Imai Y., Varela G.M., Jackson M.B., Graham M.J., Crooke R.M., Ahima R.S. Reduction of hepatosteatosis and lipid levels by an adipose differentiation-related protein antisense oligonucleotide. Gastroenterology. 2007, 132:1947-1954.
31. Magnusson B., Asp L., Bostrom P., Ruiz M., Stillemark-Billton P., Linden D., Boren J., Olofsson S.O. Adipocyte differentiation-related protein promotes fatty acid storage in cytosolic triglycerides and inhibits secretion of very low-density lipoproteins. arterioscler. Thromb. Vasc. Biol.. 2006, 26:1566-1571.
32. Chang B.H., Li L., Saha P., Chan L. Absence of adipose differentiation related protein upregulates hepatic vldl secretion, relieves hepatosteatosis, and improves whole body insulin resistance in leptin-deficient mice. J. Lipid Res. 2010, 51:2132-2142.
33. Imai Y., Boyle S., Varela G.M., Caron E., Yin X., Dhir R., Graham M.J., Ahima R.S. Effects of perilipin 2 antisense oligonucleotide treatment on hepatic lipid metabolism and gene expression. Physiol. Genom.. 2012, 44:1125-1131.
34. McManaman J.L., Bales E.S., Orlicky D.J., Jackman M., MacLean P.S., Cain S., Crunk A.E., Mansur A., Graham C.E., Bowman T.A., Greenberg A.S. Perilipin-2-null mice are protected against diet-induced obesity, adipose inflammation, and fatty liver disease. J. Lipid Res. 2013, 54:1346-1359.
35. Chang B.H., Li L., Paul A., Taniguchi S., Nannegari V., Heird W.C., Chan L. Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein. Mol. Cell. Biol.. 2006, 26:1063-1076.
36. Carr R.M., Patel R.T., Rao V., Dhir R., Graham M.J., Crooke R.M., Ahima R.S. Reduction of tip47 improves hepatic steatosis and glucose homeostasis in mice. Am. J. Physiol. Regul. integr. Comp. Physiol. 2012, 302:R996-1003.
37. Hall A.M., Brunt E.M., Chen Z., Viswakarma N., Reddy J.K., Wolins N.E., Finck B.N. Dynamic and differential regulation of proteins that coat lipid droplets in fatty liver dystrophic mice. J. Lipid Res. 2010, 51:554-563.
38. Granneman J.G., Moore H.P., Mottillo E.P., Zhu Z., Zhou L. Interactions of perilipin-(PLIN5) with adipose triglyceride lipase. J. Biol. Chem.. 2011, 286:5126-5135.
39. Zhou L., Park S.Y., Xu L., Xia X., Ye J., Su L., Jeong K.H., Hur J.H., Oh H., Tamori Y., Zingaretti C.M., Cinti S., Argente J., Yu M., Wu L., Ju S., Guan F., Yang H., Choi C.S., Savage D.B., Li P. Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged fsp27-deficient mice. Nat. Commun.. 2015, 6:5949.
40. Matsusue K., Kusakabe T., Noguchi T., Takiguchi S., Suzuki T., Yamano S., Gonzalez F.J. Hepatic steatosis in leptin-deficient mice is promoted by the ppargamma target gene fsp27. Cell Metab. 2008, 7:302-311.
41. Qu A., Taylor M., Xue X., Matsubara T., Metzger D., Chambon P., Gonzalez F.J., Shah Y.M. Hypoxia-inducible transcription factor 2alpha promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis. Hepatology 2011, 54:472-483.
42. Rankin E.B., Rha J., Selak M.A., Unger T.L., Keith B., Liu Q., Haase V.H. Hypoxia-inducible factor 2 regulates hepatic lipid metabolism. Mol. Cell. Biol. 2009, 29:4527-4538.
43. DiStefano M.T., Danai L.V., Roth Flach R.J., Chawla A., Pedersen D.J., Guilherme A., Czech M.P. The lipid droplet protein hypoxia-inducible gene 2 promotes hepatic triglyceride deposition by inhibiting lipolysis. J. Biol. Chem.. 2015, 290:15175-15184.
44. Basantani M.K., Sitnick M.T., Cai L., Brenner D.S., Gardner N.P., Li J.Z., Schoiswohl G., Yang K., Kumari M., Gross R.W., Zechner R., Kershaw E.E. Pnpla3/adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J. Lipid Res. 2011, 52:318-329.
45. Chen W., Chang B., Li L., Chan L. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology. 2010, 52:1134-1142.
46. Smagris E., BasuRay S., Li J., Huang Y., Lai K.M., Gromada J., Cohen J.C., Hobbs H.H. Pnpla3i148m knockin mice accumulate pnpla3 on lipid droplets and develop hepatic steatosis. Hepatology. 2015, 61:108-118.
47. Fujii H., Ikura Y., Arimoto J., Sugioka K., Iezzoni J.C., Park S.H., Naruko T., Itabe H., Kawada N., Caldwell S.H., Ueda M. Expression of perilipin and adipophilin in nonalcoholic fatty liver disease; relevance to oxidative injury and hepatocyte ballooning. J. Atheroscler. Thromb. 2009, 16:893-901.
48. Pawella L.M., Hashani M., Eiteneuer E., Renner M., Bartenschlager R., Schirmacher P., Straub B.K. Perilipin discerns chronic from acute hepatocellular steatosis. J. Hepatol.. 2014, 60:633-642.
49. Straub B.K., Gyoengyoesi B., Koenig M., Hashani M., Pawella L.M., Herpel E., Mueller W., Macher-Goeppinger S., Heid H., Schirmacher P. Adipophilin/perilipin-as a lipid droplet-specific marker for metabolically active cells and diseases associated with metabolic dysregulation. Histopathology. 2013, 62:617-631.
50. Magne J., Aminoff A., Perman Sundelin J., Mannila M.N., Gustafsson P., Hultenby K., Wernerson A., Bauer G., Listenberger L., Neville M.J., Karpe F., Boren J., Ehrenborg E. The minor allele of the missense polymorphism ser251pro in perilipin 2 (PLIN2) disrupts an alpha-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans. FASEB J. 2013, 27:3090-3099.
51. Dongiovanni P., Donati B., Fares R., Lombardi R., Mancina R.M., Romeo S., Valenti L. Pnpla3 i148m polymorphism and progressive liver disease. World J. Gastroenterol.. 2013, 19:6969-6978.
52. O'Shea R.S., Dasarathy S., McCullough A.J. Alcoholic liver disease. Hepatology. 2010, 51:307-328.
53. You M., Fischer M., Deeg M.A., Crabb D.W. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (srebp). J. Biol. Chem.. 2002, 277:29342-29347.
54. Siler S.Q., Neese R.A., Hellerstein M.K. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am. J. Clin. Nutr.. 1999, 70:928-936.
55. Hoek J.B., Cahill A., Pastorino J.G. Alcohol and mitochondria: A dysfunctional relationship. Gastroenterology. 2002, 122:2049-2063.
56. Wehr H., Rodo M., Lieber C.S., Baraona E. Acetaldehyde adducts and autoantibodies against vldl and ldl in alcoholics. J. Lipid Res. 1993, 34:1237-1244.
57. Carr R.M., Peralta G., Yin X., Ahima R.S. Absence of perilipin 2 prevents hepatic steatosis, glucose intolerance and ceramide accumulation in alcohol-fed mice. PLoS One 2014, 9:e97118.
58. Mak K.M., Ren C., Ponomarenko A., Cao Q., Lieber C.S. Adipose differentiation-related protein is a reliable lipid droplet marker in alcoholic fatty liver of rats. Alcohol. Clin. Exp. Res.. 2008, 32:683-689.
59. Orlicky D.J., Roede J.R., Bales E., Greenwood C., Greenberg A., Petersen D., McManaman J.L. Chronic ethanol consumption in mice alters hepatocyte lipid droplet properties. Alcohol. Clin. Exp. Res.. 2011, 35:1020-1033.
60. Carr R.M., Dhir R., Yin X., Agarwal B., Ahima R.S. Temporal effects of ethanol consumption on energy homeostasis, hepatic steatosis, and insulin sensitivity in mice. Alcohol Clin. Exp. Res.. 2013, 37:1091-1099.
61. Stickel F., Buch S., Lau K., Meyer zu Schwabedissen H., Berg T., Ridinger M., Rietschel M., Schafmayer C., Braun F., Hinrichsen H., Gunther R., Arlt A., Seeger M., Muller S., Seitz H.K., Soyka M., Lerch M., Lammert F., Sarrazin C., Kubitz R., Haussinger D., Hellerbrand C., Broring D., Schreiber S., Kiefer F., Spanagel R., Mann K., Datz C., Krawczak M., Wodarz N., Volzke H., Hampe J. Genetic variation in the pnpla3 gene is associated with alcoholic liver injury in caucasians. Hepatology. 2011, 53:86-95.
62. Tian C., Stokowski R.P., Kershenobich D., Ballinger D.G., Hinds D.A. Variant in pnpla3 is associated with alcoholic liver disease. Nat. Genet.. 2010, 42:21-23.