FoxO1 and hepatic lipid metabolism

Current Opinion in Lipidology

Volumn 20, Issue 3, 2009, Pages 217-226

  Sparks, Janet D ^a,c   Dong, Henry H ^b  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

^c UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

Akt; ApoB; Forkhead transcription factor; FoxO; Lipoproteins; Microsomal triglyceride transfer protein; Very low density lipoprotein

Indexed keywords

APOLIPOPROTEIN B; APOLIPOPROTEIN C3; INSULIN; MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN; PROTEIN KINASE B; TRANSCRIPTION FACTOR FKHR; VERY LOW DENSITY LIPOPROTEIN;

GENE EXPRESSION; GLUCOSE METABOLISM; HORMONE ACTION; HUMAN; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIPOLYSIS; LIPOPROTEIN METABOLISM; LIPOPROTEIN SECRETION; LIVER METABOLISM; METABOLIC SYNDROME X; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN DNA BINDING; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN SECRETION; REVIEW; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

EID: 67049143907     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOL.0b013e32832b3f4c     Document Type: Review

References (57)

1. Matsumoto M, Pocai A, Rossetti L, et al. Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxol in liver. Cell Metab 2007; 6:208-216.
2. Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 2004; 117:421-426.
3. Barthel A, Schmoll D, Unterman TG. FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab 2005; 16:183-189.
4. Sparks JD, Collins HL, Chirieac DV, et al. Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase. Biochem J 2006; 395:363-371.
5. Kamagate A, Qu S, Perdomo G, et al. FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. J Clin Invest 2008; 118: 2347-2364. Authors provide strong evidence that nuclear FoxO1-stimulated transcription of MTP results in enhanced VLDL production under conditions of insulin resistance.
6. Wolfrum C, Stoffel M. Coactivation of Foxa2 through Pgc-1 beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. Cell Metab 2006; 3:99-110.
7. van der Horst A, Burgering BM. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 2007; 8:440-450.
8. Maiese K, Chong ZZ, Shang YC. OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins. Trends Mol Med 2008; 14:219-227. This article discusses the role of FoxO proteins in disease and suggests the potential for new therapies targeting FoxO proteins.
9. Huang H, Tindall DJ. Dynamic FoxO transcription factors. J Cell Sci 2007; 120:2479-2487.
10. Van Der Heide LP, Hoekman MF, Smidt MP. The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 2004; 380:297-309.
11. Perrot V, Rechler MM. The coactivator p300 directly acetylates the forkhead transcription factor Foxol and stimulates Foxol-induced transcription. Mol Endocrinol 2005; 19:2283-2298.
12. Jing E, Gesta S, Kahn CR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab 2007; 6:105-114.
13. Frescas D, Valenti L, Accili D. Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J Biol Chem 2005; 280:20589-20595.
14. Daitoku H, Hatta M, Matsuzaki H, et al. Silent information regulator 2 potentiates Foxol-mediated transcription through its deacetylase activity. Proc Natl Acad Sci U S A 2004; 101:10042-10047.
15. van der Heide LP, Smidt MP. Regulation of FoxO activity by CBP/p300-mediated acetylation. Trends Biochem Sci 2005; 30:81-86.
16. Kuo M, Zilberfarb V, Gangneux N, et al. O-glycosylation of FoxO1 increases its transcriptional activity towards the glucose 6-phosphatase gene. FEBS Lett 2008; 582:829-834. This article shows that glucosamine induces O-glycosylation of FoxO1 which enhances the transcription of G6Pase, a key enzyme in hepatic glucose production, suggesting a mechanism for glucotoxicity in chronic hyperglycemia in diabetes.
17. van der Vos KE, Coffer PJ. FOXO-binding partners: it takes two to tango. Oncogene 2008; 27:2289-2299. This excellent article reviews FoxO1-binding partners and summarizes the role of interactions of FoxO1 with other transcription factors in regulation of glucose and fatty acid metabolism.
18. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007; 129:1261-1274.
19. Brownawell AM, Kops GJ, Macara IG, Burgering BM. Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX. Mol Cell Biol 2001; 21:3534-3546.
20. Ramaswamy S, Nakamura N, Sansal I, et al. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell 2002; 2:81-91.
21. Puigserver P, Rhee J, Donovan J, et al. Insulin-regulated hepatic gluconeo-genesis through FOX01-PGC-1 alpha interaction. Nature 2003; 423:550-555.
22. Dowell P, Otto TC, Adi S, Lane MD. Convergence of peroxisome proliferator-aotivated receptor gamma and Foxo1 signaling pathways. J Biol Chem 2003; 278:45485-45491.
23. Armoni M, Harel C, Kami S, et al. FOXO1 represses peroxisome proliferator-activated receptor-gamma1 and -gamma2 gene promoters in primary adipocytes. A novel paradigm to increase insulin sensitivity. J Biol Chem 2006; 281:19881-19891.
24. Qu S, Su D, Altomonte J, et al. PPARα mediates the hypolipidemic action of fibrates by antagonizing FoxO1. Am J Physiol Endocrinol Metab 2007; 292:E421-E434. This article demonstrates that nuclear FoxO1 is favored in fructose-induced insulin resistance in hamsters, which correlates with augmented hepatic apoCIII production. Treatment with fenofibrate reversed hypertriglyceridemia by functionally antagonizing FoxO1 through direct physical interaction.
25. Hatta M, Cirillo LA. Chromatin opening and stable perturbation of core histone:DNA contacts by FoxO1. J Biol Chem 2007; 282:35583-35593.
26. Davidson NO, Shelness GS. Apolipoprotein B: mRNA editing, lipoprotein assembly, and presecretory degradation. Annu Rev Nutr 2000; 20:169-193.
27. Williams KJ. Molecular processes that handle - and mishandle - dietary lipids. J Clin Invest 2008; 118:3247-3259. This is a comprehensive and beautifully illustrated review article that summarizes current knowledge of dietary lipid and intestinal lipid metabolism and details unresolved questions.
28. Fisher EA, Pan M, Chen X, et al. The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct degradative pathways. J Biol Chem 2001; 276:27855-27863.
29. Ginsberg HN, Fisher EA. The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism. J Lipid Res 2009; 50 (in press). This is an up-to-date review of the role of apoB degradation in regulating VLDL particle secretion that summarizes recent studies involving FA-induced endoplasmic reticulum stress mediated ERAD and n-3 induced PERPP degradation pathways.
30. Sparks JD, Collins HL, Sabio I, et al. Effects of fatty acids on apolipoprotein B secretion by McArdle RH-7777 rat hepatoma cells. Biochim Biophys Acta 1997; 1347:51-61.
31. Ota T, Gayet C, Ginsberg HN. Inhibition of apolipoprotein B-100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. J Clin Invest 2008; 118:316-332. Evidence is provided that oleic acid can induce endoplasmic reticulum stress in vivo and can impact levels of secretion of VLDL apoB-100 suggesting the potential for fatty acids to limit triglyceride export and contribute to hepatic steatosis development.
32. Pan M, Maitin V, Parathath S, et al. Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control. Proc Natl Acad Sci U S A 2008; 105:5862-5867. This article provides strong evidence for regulation of apoB by PERPP stimulated by polyunsaturated fatty acids. Data demonstrate that after exit from the endoplasmic reticulum, apoB undergoes PERPP following oxidant-dependent late-stage aggregation resulting in autophagosome formation and degradation of apoB in lysosomes.
33. Sparks JD, Sparks CE. Overindulgence and metabolic syndrome: is FoxO1 a missing link? J Clin Invest 2008; 118:2012-2015. A commentary on the potential role of FoxO1 in promoting hepatic overproduction of VLDL based on increased expression of MTP. The possible role of FoxO1 in short-term insulin-suppressive effects on hepatic VLDL is discussed,
34. Biddinger SB, Hernandez-Ono A, Rask-Madsen C, et al. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab 2008; 7:125-134. Loss of hepatic insulin receptors in mice is used as a model of pure hepatic insulin resistance. In these mice, there is increased hepatic VLDL production, dyslipidemia, and increased risk of atherosclerosis associated with metabolic syndrome. Results support that lack of insulin action results in augmentation of VLDL output by liver.
35. -/- mice. Am J Physiol Gastrointest Liver Physiol 2006; 291:G382-G388.
36. Hussain MM, Rava P, Pan X, et al. Microsomal triglyceride transfer protein in plasma and cellular lipid metabolism. Curr Opin Lipidol 2008; 19:277-284. This study summarizes recent advances in the regulation of MTP and its role in apoB-containing lipoprotein assembly.
37. Wetterau JR, Aggerbeck LP, Bouma ME, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 1992; 258:999-1001.
38. Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M, Wetterau JR. The role of the microsomal triglygeride transfer protein in abetalipoproteinemia. Annu Rev Nutr 2000; 20:663-697.
39. Pan M, Liang JS, Fisher EA, Ginsberg HN. The late addition of core lipids to nascent apolipoprotein B100, resulting in the assembly and secretion of triglyceride-rich lipoproteins, is independent of both microsomal triglyceride transfer protein activity and new triglyceride synthesis. J Biol Chem 2002; 277:4413-4421.
40. Wiggins D, Gibbons GF. The lipolysis/esterification cycle of hepatic triacyl-glycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas. Biochem J 1992; 284 (Pt 2):457-462.
41. Wiggins D, Gibbons GF. Origin of hepatic very-low-density lipoprotein triacylglycerol: the contribution of cellular phospholipid. Biochem J 1996; 320 (Pt 2):673-679.
42. Lass A, Zimmermann R, Haemmerle G, et al. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome. Cell Metab 2006; 3:309-319.
43. Reid BN, Abies GP, Otlivanchik OA, et al. Hepatic overexpression of hor- mone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis. J Biol Chem 2008; 283:13087-13099. Hormone-sensitive lipase and adipose triglyceride lipase are important in lipolysis of triglyceride lipid droplets, mobilization of fatty acids, and channeling them to oxidation pathways without increasing hepatic VLDL secretion.
44. Caviglia JM, Sparks JD, Toraskar N, et al. ABHD5/CGI58 facilitates the assembly and secretion of apolipoprotein B lipoproteins by McA RH7777 rat hepatoma cells. Biochim Biophys Acta 2009; 1791:198-205. Evidence is provided for the role of ABHD5/CGI58 as a cofactor for ATGL in the lipolysis component of the lipolysis/re-esterification cycle and may be involved in channeling fatty acids for VLDL triglyceride assembly and secretion.
45. Ghosh AK, Ramakrishnan G, Chandramohan C, Rajasekharan R. CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid. J Biol Chem 2008; 283:24525-24533.
46. Ledford AS, Weinberg RB, Cook VR, et al. Self-association and lipid binding properties of the lipoprotein initiating domain of apolipoprotein B. J Biol Chem 2006;281:8871-8876.
47. Manchekar M, Richardson PE, Sun Z, et al. Charged amino acid residues 997-1000 of human apolipoprotein B100 are critical for the initiation of lipoprotein assembly and the formation of a stable lipidated primordial particle in McA-RH7777 cells. J Biol Chem 2008; 283:29251-29265. Authors provide evidence for the importance of residues 717-720 and 997-1000 in the formation of the lipoprotein initiating domain of apoB possibly by a hair-pin-bridge mechanism that completes initial stages of primordial particle formation.
48. Swift LL, Zhu MY, Kakkad B, et al. Subcellular localization of microsomal triglyceride transfer protein. J Lipid Res 2003; 44:1841-1849.
49. Phung TL, Roncone A, Jensen KL, et al. Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum. J Biol Chem 1997; 272:30693-30702.
50. Fisher EA, Ginsberg HN. Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. J Biol Chem 2002; 277:17377-17380.
51. Brodsky JL, Fisher EA. The many intersecting pathways underlying apolipo- protein B secretion and degradation. Trends Endocrinol Metab 2008; 19:254-259. This is an excellent review article on how VLDL secretion by liver is regulated by apoB degradation pathways with a focus on endoplasmic reticulum-associated degradation and autophagy.
52. Kamagate A, Dong HH. FoxO1 integrates insulin signaling to VLDL produc-tion. Cell Cycle 2008; 7:3162-3170. This is an excellent review of FoxO1 in hepatic VLDL metabolism supporting the idea that FoxO1 is involved in insulin regulation of hepatic production and VLDL metabolism in parallel mechanisms with hepatic glucose production with both involving transcriptional regulation.
53. Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene 2008; 27:2320-2336. This review of FoxO1 contains a summary of FoxO1 gain and loss of function studies in hepatic lipid metabolism.
54. Zhang W, Patil S, Chauhan B, et al. FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression. J Biol Chem 2006; 281:10105-10117.
55. Pan X, Hussain MM. Diurnal regulation of microsomal triglyceride transfer protein and plasma lipid levels. J Biol Chem 2007; 282:24707-24719. This article presents surprising evidence demonstrating that hepatic and intestinal MTP activity, MTP protein levels and plasma lipid levels undergo diurnal regulation and are affected by environmental factors such as food and light. MTP changes are associated with changes in mttp gene transcription.
56. Sparks JD, Sparks CE, Bolognino M, et al. Effects of nonketotic streptozotocin diabetes on apolipoprotein B synthesis and secretion by primary cultures of rat hepatocytes. J Clin Invest 1988; 82:37-43.
57. Ji C, Shinohara M, Kuhlenkamp J, et al. Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes. Hepatology 2007; 46:1586-1596.