Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin resistance by inducing fibroblast growth factor 21

Hepatology

Volumn 61, Issue 6, 2015, Pages 1908-1919

  Lu, Peipei ^a   Yan, Jiong ^a   Liu, Ke ^a   Garbacz, Wojciech G ^a   Wang, Pengcheng ^a   Xu, Meishu ^a   Ma, Xiaochao ^a   Xie, Wen ^a,b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 METHYLCHOLANTHRENE; ACC1 PROTEIN; ADIPONECTIN; ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; AROMATIC HYDROCARBON RECEPTOR; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; FAS ANTIGEN; FAT DROPLET; FATTY ACID; FIBROBLAST GROWTH FACTOR 21; GLUCOSE; INTERLEUKIN 6; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; SCD1 PROTEIN; SHORT HAIRPIN RNA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN; FIBROBLAST GROWTH FACTOR;

ADENOVIRIDAE; ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DIET INDUCED OBESITY; DISEASE EXACERBATION; EMBRYO; ENERGY METABOLISM; ENZYME PHOSPHORYLATION; FAT MASS; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; FATTY LIVER; FOOD INTAKE; GENE EXPRESSION; GENE SILENCING; GLUCOSE TOLERANCE; GLUCOSE TOLERANCE TEST; HUMAN; INSULIN ALLERGY; INSULIN RESISTANCE; INSULIN TOLERANCE TEST; INTRAABDOMINAL FAT; LIGAND BINDING; LIVER INJURY; LYMPHOCYTIC INFILTRATION; MARKER GENE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PHENOTYPE; PLEIOTROPY; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN FUNCTION; SKELETAL MUSCLE; TRANSACTIVATION; ADVERSE EFFECTS; ANIMAL; LIPID DIET; METABOLISM; TRANSGENIC MOUSE;

ANIMALS; DIET, HIGH-FAT; FATTY LIVER; FIBROBLAST GROWTH FACTORS; GENE KNOCKDOWN TECHNIQUES; GENETIC PLEIOTROPY; HUMANS; INSULIN RESISTANCE; MICE, TRANSGENIC; OBESITY; RECEPTORS, ARYL HYDROCARBON;

EID: 84929590501     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.27719     Document Type: Article

References (38)

1. Remillard RB, Bunce NJ. Linking dioxins to diabetes: epidemiology and biologic plausibility. Environ Health Perspect 2002;110:853-858.
2. Lee JH, Wada T, Febbraio M, He J, Matsubara T, Lee MJ, et al. A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis. Gastroenterology 2010;139:653-663.
3. Utzschneider KM, Kahn SE. The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006;91:4753-4761.
4. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829-838.
5. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004;114:147-152.
6. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116:1793-1801.
7. Sun Z, Lazar MA. Dissociating fatty liver and diabetes. Trends Endocrinol Metab 2013;24:4-12.
8. Stefan N, Kantartzis K, Haring HU. Causes and metabolic consequences of fatty liver. Endocr Rev 2008;29:939-960.
9. Heijboer AC, Donga E, Voshol PJ, Dang ZC, Havekes LM, Romijn JA, et al. Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice. J Lipid Res 2005;46:582-588.
10. Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2004;19:537-544.
11. Lu H, Cui W, Klaassen CD. Nrf2 protects against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative injury and steatohepatitis. Toxicol Appl Pharmacol 2011;256:122-135.
12. Kliewer SA, Mangelsdorf DJ. Fibroblast growth factor 21: from pharmacology to physiology. Am J Clin Nutr 2010;91:254S-257S.
13. Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab 2007;5:426-437.
14. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, et al. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab 2007;5:415-425.
15. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, et al. FGF-21 as a novel metabolic regulator. J Clin Invest 2005;115:1627-1635.
16. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H, Toma D, et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 2006;281:15013-15020.
17. Gao J, He J, Zhai Y, Wada T, Xie W. The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity. J Biol Chem 2009;284:25984-25992.
18. McGuire J, Okamoto K, Whitelaw ML, Tanaka H, Poellinger L. Definition of a dioxin receptor mutant that is a constitutive activator of transcription: delineation of overlapping repression and ligand binding functions within the PAS domain. J Biol Chem 2001;276:41841-41849.
19. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011;332:1519-1523.
20. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-1808.
21. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002;8:731-737.
22. Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 2009;9:407-416.
23. Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, et al. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun 2006;340:291-295.
24. Erion DM, Shulman GI. Diacylglycerol-mediated insulin resistance. Nat Med 2010;16:400-402.
25. Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 2006;45:42-72.
26. Lin Z, Tian H, Lam KS, Lin S, Hoo RC, Konishi M, et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab 2013;17:779-789.
27. Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci USA 2010;107:12553-12558.
28. Sun Z, Miller RA, Patel RT, Chen J, Dhir R, Wang H, et al. Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nat Med 2012;18:934-942.
29. Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab 2007;6:69-78.
30. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 2005;11:191-198.
31. Potthoff MJ, Inagaki T, Satapati S, Ding X, He T, Goetz R, et al. FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proc Natl Acad Sci USA 2009;106:10853-10858.
32. Fisher FM, Chui PC, Nasser IA, Popov Y, Cunniff JC, Lundasen T, et al. Fibroblast growth factor 21 limits lipotoxicity by promoting hepatic fatty acid activation in mice on methionine and choline-deficient diets. Gastroenterology 2014;147:1073-1083.
33. Fernandez-Salguero PM, Hilbert DM, Rudikoff S, Ward JM, Gonzalez FJ. Aryl-hydrocarbon receptor-deficient mice are resistant to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced toxicity. Toxicol Appl Pharmacol 1996;140:173-179.
34. Schmidt JV, Su GH, Reddy JK, Simon MC, Bradfield CA. Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci USA 1996;93:6731-6736.
35. Beischlag TV, Luis Morales J, Hollingshead BD, Perdew GH. The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 2008;18:207-250.
36. Nguyen LP, Bradfield CA. The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol 2008;21:102-116.
37. Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, et al. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 2007;446:562-566.
38. Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010;329:1345-1348.