A new mechanism of thyroid hormone receptor β agonists ameliorating nonalcoholic steatohepatitis by inhibiting intestinal lipid absorption via remodeling bile acid profiles

Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77:1335–47.

Article  PubMed  Google Scholar 

Xu X, Poulsen KL, Wu L, Liu S, Miyata T, Song Q, et al. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Signal Transduct Target Ther. 2022;7:287. https://doi.org/10.1038/s41392-022-01119-3.

Article  PubMed  PubMed Central  Google Scholar 

Hodson L, Gunn PJ. The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state. Nat Rev Endocrinol. 2019;15:689–700.

Article  CAS  PubMed  Google Scholar 

Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021;184:2537–64.

Article  CAS  PubMed  Google Scholar 

Abenavoli L, Boccuto L, Federico A, Dallio M, Loguercio C, Di Renzo L, et al. Diet and non-alcoholic fatty liver disease: the mediterranean way. Int J Environ Res Public Health. 2019;16:3011. https://doi.org/10.3390/ijerph16173011.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huby T, Gautier EL. Immune cell-mediated features of non-alcoholic steatohepatitis. Nat Rev Immunol. 2022;22:429–43.

Article  CAS  PubMed  Google Scholar 

Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94:355–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ritter MJ, Amano I, Hollenberg AN. Thyroid hormone signaling and the liver. Hepatology. 2020;72:742–52.

Article  CAS  PubMed  Google Scholar 

Kelly MJ, Pietranico-Cole S, Larigan JD, Haynes NE, Reynolds CH, Scott N, et al. Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a highly selective thyroid hormone receptor β agonist in clinical trials for the treatment of dyslipidemia. J Med Chem. 2014;57:3912–23.

Article  CAS  PubMed  Google Scholar 

Harrison SA, Taub R, Neff GW, Lucas KJ, Labriola D, Moussa SE, et al. Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2023;29:2919–28.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sinha RA, Singh BK, Yen PM. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol. 2018;14:259–69.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sinha RA, Singh BK, Zhou J, Wu Y, Farah BL, Ohba K, et al. Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling. Autophagy. 2015;11:1341–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sinha RA, Bruinstroop E, Singh BK, Yen PM. Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists. Thyroid. 2019;29:1173–91.

Article  CAS  PubMed  Google Scholar 

Li T, Chiang JY. Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res. 2009;2009:501739. https://doi.org/10.1155/2009/501739.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chiang JY. Bile acid metabolism and signaling. Compr Physiol. 2013;3:1191–212.

Article  PubMed  PubMed Central  Google Scholar 

Li-Hawkins J, Gåfvels M, Olin M, Lund EG, Andersson U, Schuster G, et al. Cholic acid mediates negative feedback regulation of bile acid synthesis in mice. J Clin Invest. 2002;110:1191–200.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expr. 2018;18:71–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jia W, Wei M, Rajani C, Zheng X. Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell. 2021;12:411–25.

Article  CAS  PubMed  Google Scholar 

Lin JZ, Martagon AJ, Hsueh WA, Baxter JD, Gustafsson JA, Webb P, et al. Thyroid hormone receptor agonists reduce serum cholesterol independent of the LDL receptor. Endocrinology. 2012;153:6136–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bonde Y, Breuer O, Lutjohann D, Sjoberg S, Angelin B, Rudling M. Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans. J Lipid Res. 2014;55:2408–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Johansson L, Rudling M, Scanlan TS, Lundåsen T, Webb P, Baxter J, et al. Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice. Proc Natl Acad Sci USA. 2005;102:10297–302.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berkenstam A, Kristensen J, Mellström K, Carlsson B, Malm J, Rehnmark S, et al. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. Proc Natl Acad Sci USA. 2008;105:663–7.

Article  CAS  PubMed  Google Scholar 

Astapova I, Ramadoss P, Costa-e-Sousa RH, Ye F, Holtz KA, Li Y, et al. Hepatic nuclear corepressor 1 regulates cholesterol absorption through a TRbeta1-governed pathway. J Clin Invest. 2014;124:1976–86.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yan Y, Niu Z, Sun C, Li P, Shen S, Liu S, et al. Hepatic thyroid hormone signalling modulates glucose homeostasis through the regulation of GLP-1 production via bile acid-mediated FXR antagonism. Nat Commun. 2022;13:6408. https://doi.org/10.1038/s41467-022-34258-w.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53:810–20.

Article  CAS  PubMed  Google Scholar 

Liang W, Menke AL, Driessen A, Koek GH, Lindeman JH, Stoop R, et al. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology. PLoS One. 2014;9:e115922. https://doi.org/10.1371/journal.pone.0115922.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarafian MH, Lewis MR, Pechlivanis A, Ralphs S, Mcphail MJW, Patel VC, et al. Bile acid profiling and quantification in biofluids using ultra-performance liquid chromatography tandem mass spectrometry. Anal Chem. 2015;87:9662–70.

Article  CAS  PubMed  Google Scholar 

Cajka T, Smilowitz JT, Fiehn O. Validating quantitative untargeted lipidomics across nine liquid chromatographyhigh-resolution mass spectrometry platforms. Anal Chem. 2017;89:12360–8.

Article  CAS  PubMed  Google Scholar 

Jin HR, Wang J, Wang ZJ, Xi MJ, Xia BH, Deng K, et al. Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics. J Hematol Oncol. 2023;16:103. https://doi.org/10.1186/s13045-023-01498-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clifford BL, Sedgeman LR, Williams KJ, Morand P, Cheng A, Jarrett KE, et al. FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption. Cell Metab. 2021;33:1671–84.e4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Malcicka M, Visser B, Ellers J. An evolutionary perspective on linoleic acid synthesis in animals. Evol Biol. 2018;45:15–26.

Article  PubMed  Google Scholar 

Chiang JYL, Ferrell JM. Bile acids as metabolic regulators and nutrient sensors. Annu Rev Nutr. 2019;39:175–200.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chiang JY. Bile acids: regulation of synthesis. J Lipid Res. 2009;50:1955–66.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li T, Chiang JY. Nuclear receptors in bile acid metabolism. Drug Metab Rev. 2013;45:145–55.

Article  CAS 

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