Complex Interplay between the Lipin 1 and the Hepatocyte Nuclear Factor 4 α (HNF4α) Pathways to Regulate Liver Lipid Metabolism

PLoS ONE

Volumn 7, Issue 12, 2012, Pages

  Chen, Zhouji ^a   Gropler, Matthew C ^a   Mitra, Mayurranjan S ^a   Finck, Brian N ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN C3; APOPROTEIN; APOPROTEIN A4; CELL PROTEIN; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; LIPIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; FATTY ACID OXIDATION; GAIN OF FUNCTION MUTATION; GENE; GENE ACTIVATION; GENE EXPRESSION; GENE INDUCTION; GENE REPRESSION; GENE TARGETING; HUMAN; HUMAN CELL; INTRON; LIPID LIVER LEVEL; LIPID METABOLISM; LIPIN 1 GENE; LIVER CELL; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; PROMOTER REGION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM;

ANALYSIS OF VARIANCE; ANIMALS; BLOTTING, WESTERN; CHROMATIN IMMUNOPRECIPITATION; DNA PRIMERS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HEK293 CELLS; HEP G2 CELLS; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; IMMUNOPRECIPITATION; LIPID METABOLISM; LIVER; LUCIFERASES; MICE; MICE, INBRED C57BL; NUCLEAR PROTEINS; PHOSPHATIDATE PHOSPHATASE; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TRANS-ACTIVATORS;

EID: 84870874579     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0051320     Document Type: Article

References (46)

1. Reue K, Zhang P (2007) The lipin protein family: Dual roles in lipid biosynthesis and gene expression. FEBS Lett.
2. Chen Z, Gropler MC, Norris J, Lawrence JC Jr, Harris TE, et al. (2008) Alterations in hepatic metabolism in fld mice reveal a role for lipin 1 in regulating VLDL-triacylglyceride secretion. Arterioscler Thromb Vasc Biol 28: 1738-1744.
3. Croce MA, Eagon JC, LaRiviere LL, Korenblat KM, Klein S, et al. (2007) Hepatic lipin 1beta expression is diminished in insulin-resistant obese subjects and is reactivated by marked weight loss. Diabetes 56: 2395-2399.
4. Harris TE, Huffman TA, Chi A, Shabanowitz J, Hunt DF, et al. (2007) Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1. J Biol Chem 282: 277-286.
5. Han GS, Wu WI, Carman GM, (2006) The Saccharomyces cerevisiae Lipin homolog is a Mg2+-dependent phosphatidate phosphatase enzyme. J Biol Chem 281: 9210-9218.
6. Donkor J, Sariahmetoglu M, Dewald J, Brindley DN, Reue K, (2007) Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. J Biol Chem 282: 3450-3457.
7. Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S, (2005) The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth. Embo J 24: 1931-1941.
8. Péterfy M, Phan J, Xu P, Reue K, (2001) Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat Genet 27: 121-124.
9. Peterfy M, Phan J, Reue K, (2005) Alternatively spliced lipin isoforms exhibit distinct expression pattern, subcellular localization, and role in adipogenesis. J Biol Chem 280: 32883-32889.
10. Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, et al. (2006) Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway. Cell Metab 4: 199-210.
11. Kim HB, Kumar A, Wang L, Liu GH, Keller SR, et al. (2010) Lipin 1 represses NFATc4 transcriptional activity in adipocytes to inhibit secretion of inflammatory factors. Mol Cell Biol 30: 3126-3139.
12. Chen Z, Fitzgerald RL, Averna MR, Schonfeld G, (2000) A targeted apolipoprotein B-38.9-producing mutation causes fatty livers in mice due to the reduced ability of apolipoprotein B-38.9 to transport triglycerides. J Biol Chem 275: 32807-32815.
13. Mitra MS, Schilling JD, Wang X, Jay PY, Huss JM, et al. (2011) Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor γ coactivator 1α/estrogen related receptor axis J Mol Cell Cardiol. 51: 120-128.
14. Leone TC, Cresci S, Carter ME, Zhang Z, Lala DS, et al. (1995) The human medium chain acyl-CoA dehydrogenase gene promoter consists of a complex arrangement of nuclear receptor response elements and Sp1 binding sites. J Biol Chem 270: 24622.
15. Pineda Torra I, Jamshidi Y, Flavell DM, Fruchart J-C, Staels B, (2002) Characterization of the Human PPAR{alpha} Promoter: Identification of a Functional Nuclear Receptor Response Element. Mol Endocrinol 16: 1013-1028.
16. Rhee J, Ge H, Yang W, Fan M, Handschin C, et al. (2006) Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism. J Biol Chem 281: 14683-14690.
17. Carrier JC, Deblois G, Champigny C, Levy E, Giguere V, (2004) Estrogen-related receptor alpha (ERRalpha) is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine. J Biol Chem 279: 52052-52058.
18. Carter ME, Gulick T, Raisher BD, Caira T, Ladias JA, et al. (1993) Hepatocyte nuclear factor-4 activates medium chain acyl-CoA dehydrogenase gene transcription by interacting with a complex regulatory element. J Biol Chem 268: 13805-13810.
19. Kressler D, Schreiber SN, Knutti D, Kralli A, (2002) The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha. J Biol Chem 277: 13918-13925.
20. Ponugoti B, Fang S, Kemper JK, (2007) Functional interaction of hepatic nuclear factor-4 and peroxisome proliferator-activated receptor-gamma coactivator 1alpha in CYP7A1 regulation is inhibited by a key lipogenic activator, sterol regulatory element-binding protein-1c. Mol Endocrinol 21: 2698-2712.
21. Gropler MC, Harris TE, Hall AM, Wolins NE, Gross RW, et al. (2009) Lipin 2 is a liver-enriched phosphatidate phosphohydrolase enzyme that is dynamically regulated by fasting and obesity in mice. J Biol Chem 284: 6763-6772.
22. Zhang P, O'Loughlin L, Brindley DN, Reue K (2008) Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis. J Lipid Res.
23. Pearen MA, Myers SA, Raichur S, Ryall JG, Lynch GS, et al. (2008) The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle. Endocrinology 149: 2853-2865.
24. Koh YK, Lee MY, Kim JW, Kim M, Moon JS, et al. (2008) Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2. J Biol Chem 283: 34896-34906.
25. Ryu D, Oh KJ, Jo HY, Hedrick S, Kim YN, et al. (2009) TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1. Cell Metab 9: 240-251.
26. Huss JM, Torra IP, Staels B, Giguere V, Kelly DP, (2004) Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol 24: 9079-9091.
27. Huss JM, Kopp RP, Kelly DP, (2002) Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and-gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem 277: 40265-40274.
28. Lin J, Tarr PT, Yang R, Rhee J, Puigserver P, et al. (2003) PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem 278: 30843-30848.
29. Yin L, Ma H, Ge X, Edwards PA, Zhang Y, (2011) Hepatic hepatocyte nuclear factor 4alpha is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler Thromb Vasc Biol 31: 328-336.
30. Lai CQ, Parnell LD, Ordovas JM, (2005) The APOA1/C3/A4/A5 gene cluster, lipid metabolism and cardiovascular disease risk. Curr Opin Lipidol 16: 153-166.
31. Sladek FM, Zhong WM, Lai E, Darnell JE Jr, (1990) Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 4: 2353-2365.
32. Sheena V, Hertz R, Nousbeck J, Berman I, Magenheim J, et al. (2005) Transcriptional regulation of human microsomal triglyceride transfer protein by hepatocyte nuclear factor-4alpha. J Lipid Res 46: 328-341.
33. Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ, (2001) Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21: 1393-1403.
34. Battle MA, Konopka G, Parviz F, Gaggl AL, Yang C, et al. (2006) Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. Proc Natl Acad Sci U S A 103: 8419-8424.
35. Bolotin E, Liao H, Ta TC, Yang C, Hwang-Verslues W, et al. (2010) Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays. Hepatology 51: 642-653.
36. Huss JM, Kelly DP, (2004) Nuclear receptor signaling and cardiac energetics. Circ Res 95: 568-578.
37. Puigserver P, Wu Z, Park CW, Graves R, Wright M, et al. (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92: 829-839.
38. Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM, (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8: 1224-1234.
39. Langner CA, Birkenmeier EH, Ben-Zeev O, Schotz MC, Sweet HO, et al. (1989) The fatty liver dystrophy (fld) mutation. A new mutant mouse with a developmental abnormality in triglyceride metabolism and associated tissue-specific defects in lipoprotein lipase and hepatic lipase activities. J Biol Chem 264: 7994-8003.
40. Ladias JA, Hadzopoulou-Cladaras M, Kardassis D, Cardot P, Cheng J, et al. (1992) Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3. J Biol Chem 267: 15849-15860.
41. Ktistaki E, Lacorte JM, Katrakili N, Zannis VI, Talianidis I, (1994) Transcriptional regulation of the apolipoprotein A-IV gene involves synergism between a proximal orphan receptor response element and a distant enhancer located in the upstream promoter region of the apolipoprotein C-III gene. Nucleic Acids Res 22: 4689-4696.
42. Hanniman EA, Lambert G, Inoue Y, Gonzalez FJ, Sinal CJ, (2006) Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. J Lipid Res 47: 2503-2514.
43. Zannis VI, Kan HY, Kritis A, Zanni E, Kardassis D, (2001) Transcriptional regulation of the human apolipoprotein genes. Front Biosci 6: D456-504.
44. Ebara T, Ramakrishnan R, Steiner G, Shachter NS, (1997) Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E-null mice. Apolipoprotein CIII-induced hypertriglyceridemia is not mediated by effects on apolipoprotein E. J Clin Invest 99: 2672-2681.
45. Hirano T, Takahashi T, Saito S, Tajima H, Ebara T, et al. (2001) Apoprotein C-III deficiency markedly stimulates triglyceride secretion in vivo: comparison with apoprotein E. Am J Physiol Endocrinol Metab. 281: E665-669.
46. Duverger N, Tremp G, Caillaud JM, Emmanuel F, Castro G, et al. (1996) Protection against atherogenesis in mice mediated by human apolipoprotein A-IV. Science 273: 966-968.