HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation.
fibrosis
high-density lipoproteins
inflammation
liver X receptors
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
05
04
2020
revised:
08
10
2020
accepted:
12
10
2020
pubmed:
25
10
2020
medline:
22
6
2021
entrez:
24
10
2020
Statut:
ppublish
Résumé
Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl After CCl Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy.
Sections du résumé
BACKGROUND AND AIMS
Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects.
METHODS
Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl
RESULTS
After CCl
CONCLUSIONS
Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy.
Substances chimiques
Cholesterol, HDL
0
Liver X Receptors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3127-3139Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Lee YA, Wallace MC, Friedman SL. Pathobiology of liver fibrosis: a translational success story. Gut. 2015;64(5):830-841. PubMed PMID: 25681399. Pubmed Central PMCID: 4477794.
Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study. BMJ. 2018;362:1999-2016. PubMed PMID: 30021785. Pubmed Central PMCID: 6050518.
Seki E, Schwabe RF. Hepatic inflammation and fibrosis: Functional links and key pathways. Hepatology. 2015;61(3):1066-1079. PubMed PMID: 25066777. Pubmed Central PMCID: 4306641.
Marra F, Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol. 2018;68(2):280-295. PubMed PMID: 29154964.
Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019;394(10215):2184-2196. PubMed PMID: 31813633.
Janowski BA, Grogan MJ, Jones SA, et al. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA. 1999;96(1):266-271. PubMed PMID: 9874807. Pubmed Central PMCID: 15128.
Calkin AC, Tontonoz P. Liver x receptor signaling pathways and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30(8):1513-1518. PubMed PMID: 20631351. Pubmed Central PMCID: 2919217.
Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest. 2006;116(3):607-614. PubMed PMID: 16511593. Pubmed Central PMCID: 1386115.
Schulman IG. Liver X receptors link lipid metabolism and inflammation. FEBS Lett. 2017;591(19):2978-2991. PubMed PMID: 28555747. Pubmed Central PMCID: 5638683.
Fessler MB. The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease. Pharmacol Ther. 2018;181:1-12. PubMed PMID: 28720427. Pubmed Central PMCID: 5743771.
Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res. 2004;95(8):764-772. PubMed PMID: 15486323.
De Nardo D, Labzin LI, Kono H, et al. High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol. 2014;15(2):152-160. PubMed PMID: 24317040. Pubmed Central PMCID: 4009731.
Thabut D, Tazi KA, Bonnefont-Rousselot D, et al. High-density lipoprotein administration attenuates liver proinflammatory response, restores liver endothelial nitric oxide synthase activity, and lowers portal pressure in cirrhotic rats. Hepatology. 2007;46(6):1893-1906. PubMed PMID: 17918268.
Galbois A, Thabut D, Tazi KA, et al. Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis. Hepatology. 2009;49(1):175-184. PubMed PMID: 19053046.
Trieb M, Rainer F, Stadlbauer V, et al. HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure. J Hepatol. 2020;73(1):113-120.
Hijmans BS, Tiemann CA, Grefhorst A, et al. A systems biology approach reveals the physiological origin of hepatic steatosis induced by liver X receptor activation. FASEB J. 2015;29(4):1153-1164. PubMed PMID: 25477282.
Brunham LR, Kruit JK, Iqbal J, et al. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest. 2006;116(4):1052-1062. PubMed PMID: 16543947. Pubmed Central PMCID: 1401485.
Lo Sasso G, Murzilli S, Salvatore L, et al. Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. Cell Metab. 2010;12(2):187-193. PubMed PMID: 20674863.
Peng D, Hiipakka RA, Dai Q, et al. Antiatherosclerotic effects of a novel synthetic tissue-selective steroidal liver X receptor agonist in low-density lipoprotein receptor-deficient mice. J Pharmacol Exp Ther. 2008;327(2):332-342. PubMed PMID: 18723776. Pubmed Central PMCID: 2574974.
De Minicis S, Rychlicki C, Agostinelli L, et al. Semaphorin 7A contributes to TGF-beta-mediated liver fibrogenesis. Am J Pathol. 2013;183(3):820-830. PubMed PMID: 23850082. Pubmed Central PMCID: 5819760.
Luedde T, Schwabe RF. NF-kappaB in the liver-linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2011;8(2):108-118. PubMed PMID: 21293511. Pubmed Central PMCID: 3295539.
Pradere JP, Troeger JS, Dapito DH, Mencin AA, Schwabe RF. Toll-like receptor 4 and hepatic fibrogenesis. Semin Liver Dis. 2010;30(03):232-244. PubMed PMID: 20665376. Pubmed Central PMCID: 4099360.
Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol. 2013;59(3):583-594. PubMed PMID: 23567086.
De Minicis S, Seki E, Paik YH, et al. Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis. Hepatology. 2010;52:1420-1430. PubMed PMID: 20690191. Pubmed Central PMCID: 2947612.
Koyama Y, Brenner DA. Liver inflammation and fibrosis. J Clin Invest. 2017;127(1):55-64. PubMed PMID: 28045404. Pubmed Central PMCID: 5199698.
Barikbin R, Neureiter D, Wirth J, et al. Induction of heme oxygenase 1 prevents progression of liver fibrosis in Mdr2 knockout mice. Hepatology. 2012;55(2):553-562. PubMed PMID: 21953613.
Baroni GS, D'Ambrosio L, Curto P, et al. Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology. 1996;23(5):1189-1199. PubMed PMID: 8621153.
Seki E, De Minicis S, Osterreicher CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 2007;13(11):1324-1332. PubMed PMID: 17952090.
Yang YM, Seki E. TNFalpha in liver fibrosis. Curr Pathobiol Rep. 2015;3(4):253-261. PubMed PMID: 26726307. Pubmed Central PMCID: 4693602.
Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445-455. PubMed PMID: 23619691. Pubmed Central PMCID: 3725458.
Ganesan LP, Mates JM, Cheplowitz AM, et al. Scavenger receptor B1, the HDL receptor, is expressed abundantly in liver sinusoidal endothelial cells. Scientific Rep. 2016;6:20646. PubMed PMID: 26865459. Pubmed Central PMCID: 4749959.
Paik YH, Iwaisako K, Seki E, et al. The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91(phox) mediate hepatic fibrosis in mice. Hepatology. 2011;53(5):1730-1741. PubMed PMID: 21384410. Pubmed Central PMCID: 3082608.
Malerod L, Juvet K, Gjoen T, Berg T. The expression of scavenger receptor class B, type I (SR-BI) and caveolin-1 in parenchymal and nonparenchymal liver cells. Cell Tissue Res. 2002;307(2):173-180. PubMed PMID: 11845324.
Soares MP, Bach FH. Heme oxygenase-1: from biology to therapeutic potential. Trends Mol Med. 2009;15(2):50-58. PubMed PMID: 19162549.
Shen WJ, Azhar S, Kraemer FB, SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu Rev Physiol. 2018;80(1):95-116. PubMed PMID: 29125794. Pubmed Central PMCID: 6376870.
Bonamassa B, Moschetta A. Atherosclerosis: lessons from LXR and the intestine. Trends Endocrinol Metab. 2013;24(3):120-128. PubMed PMID: 23158108.
Benitez-Santana T, Hugo SE, Schlegel A. Role of intestinal LXRalpha in regulating post-prandial lipid excursion and diet-induced hypercholesterolemia and hepatic lipid accumulation. Front Physiol. 2017;8:280. PubMed PMID: 28536535. Pubmed Central PMCID: 5422522.