Liver Injury and Cell Survival in Non-Alcoholic Steatohepatitis Regulated by Sex-Based Difference Through B Cell Lymphoma 6

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Dec 11

PMID 36497010

Authors

Akihide Kamiya

Kinuyo Ida

Affiliations

Soon will be listed here.

Abstract

The liver is a crucial organ for maintaining homeostasis in living organisms and is the center of various metabolic functions. Therefore, abnormal metabolic activity, as in metabolic syndrome, leads to pathological conditions, such as abnormal accumulation of lipids in the liver. Inflammation and cell death are induced by several stresses in the fatty liver, namely steatohepatitis. In recent years, an increase in non-alcoholic steatohepatitis (NASH), which is not dependent on excessive alcohol intake, has become an issue as a major cause of liver cirrhosis and liver cancer. There are several recent findings on functional sex-based differences, NASH, and cell stress and death in the liver. In particular, NASH-induced liver injury and tumorigeneses were suppressed by B cell lymphoma 6, the transcriptional factor regulating sex-based liver functional gene expression. In this review, we discuss cell response to stress and lipotoxicity in NASH and its regulatory mechanisms.

Citing Articles

B Cell Lymphoma 6 (BCL6): A Conserved Regulator of Immunity and Beyond.

Liongue C, Almohaisen F, Ward A Int J Mol Sci. 2024; 25(20).

PMID: 39456751 PMC: 11507070. DOI: 10.3390/ijms252010968.

References

Bell L, Wang J, Muralidharan S, Chalasani S, Fullenkamp A, Wilson L . Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: a pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trial follow-up.... Hepatology. 2012; 56(4):1311-8. PMC: 3432683. DOI: 10.1002/hep.25805. View

Sharma M, Premkumar M, Kulkarni A, Kumar P, Reddy D, Rao N . Drugs for Non-alcoholic Steatohepatitis (NASH): Quest for the Holy Grail. J Clin Transl Hepatol. 2021; 9(1):40-50. PMC: 7868704. DOI: 10.14218/JCTH.2020.00055. View

Waxman D, OConnor C . Growth hormone regulation of sex-dependent liver gene expression. Mol Endocrinol. 2006; 20(11):2613-29. DOI: 10.1210/me.2006-0007. View

Postic C, Magnuson M . DNA excision in liver by an albumin-Cre transgene occurs progressively with age. Genesis. 2000; 26(2):149-50. DOI: 10.1002/(sici)1526-968x(200002)26:2<149::aid-gene16>3.0.co;2-v. View

Tsurusaki S, Tsuchiya Y, Koumura T, Nakasone M, Sakamoto T, Matsuoka M . Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis. Cell Death Dis. 2019; 10(6):449. PMC: 6579767. DOI: 10.1038/s41419-019-1678-y. View

Yoshida T, Fukuda T, Hatano M, Koseki H, Okabe S, Ishibashi K . The role of Bcl6 in mature cardiac myocytes. Cardiovasc Res. 1999; 42(3):670-9. DOI: 10.1016/s0008-6363(99)00007-3. View

Kaji T, Ishige A, Hikida M, Taka J, Hijikata A, Kubo M . Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J Exp Med. 2012; 209(11):2079-97. PMC: 3478929. DOI: 10.1084/jem.20120127. View

Sugathan A, Waxman D . Genome-wide analysis of chromatin states reveals distinct mechanisms of sex-dependent gene regulation in male and female mouse liver. Mol Cell Biol. 2013; 33(18):3594-610. PMC: 3753870. DOI: 10.1128/MCB.00280-13. View

Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal W, Strowig T . Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012; 482(7384):179-85. PMC: 3276682. DOI: 10.1038/nature10809. View

10.

Hirano K, Kuwasako T, Nakagawa-Toyama Y, Janabi M, Yamashita S, Matsuzawa Y . Pathophysiology of human genetic CD36 deficiency. Trends Cardiovasc Med. 2003; 13(4):136-41. DOI: 10.1016/s1050-1738(03)00026-4. View

11.

Rahman K, Desai C, Iyer S, Thorn N, Kumar P, Liu Y . Loss of Junctional Adhesion Molecule A Promotes Severe Steatohepatitis in Mice on a Diet High in Saturated Fat, Fructose, and Cholesterol. Gastroenterology. 2016; 151(4):733-746.e12. PMC: 5037035. DOI: 10.1053/j.gastro.2016.06.022. View

12.

Chikada H, Ida K, Nishikawa Y, Inagaki Y, Kamiya A . Liver-specific knockout of B cell lymphoma 6 suppresses progression of non-alcoholic steatohepatitis in mice. Sci Rep. 2020; 10(1):9704. PMC: 7297717. DOI: 10.1038/s41598-020-66539-z. View

13.

Khristi V, Ratri A, Ghosh S, Pathak D, Borosha S, Dai E . Disruption of ESR1 alters the expression of genes regulating hepatic lipid and carbohydrate metabolism in male rats. Mol Cell Endocrinol. 2019; 490:47-56. DOI: 10.1016/j.mce.2019.04.005. View

14.

Han Y, Choi H, Kim H, Lee M . Chemotactic cytokines secreted from Kupffer cells contribute to the sex-dependent susceptibility to non-alcoholic fatty liver diseases in mice. Life Sci. 2022; 306:120846. DOI: 10.1016/j.lfs.2022.120846. View

15.

Villa A, Della Torre S, Stell A, Cook J, Brown M, Maggi A . Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition. Proc Natl Acad Sci U S A. 2012; 109(29):11806-11. PMC: 3406808. DOI: 10.1073/pnas.1205797109. View

16.

Meda C, Barone M, Mitro N, Lolli F, Pedretti S, Caruso D . Hepatic ERα accounts for sex differences in the ability to cope with an excess of dietary lipids. Mol Metab. 2020; 32:97-108. PMC: 6957843. DOI: 10.1016/j.molmet.2019.12.009. View

17.

Chowen J, Frago L, Argente J . The regulation of GH secretion by sex steroids. Eur J Endocrinol. 2004; 151 Suppl 3:U95-100. DOI: 10.1530/eje.0.151u095. View

18.

Gao H, Falt S, Sandelin A, Gustafsson J, Dahlman-Wright K . Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver. Mol Endocrinol. 2007; 22(1):10-22. PMC: 5419629. DOI: 10.1210/me.2007-0121. View

19.

Younossi Z, Ratziu V, Loomba R, Rinella M, Anstee Q, Goodman Z . 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. DOI: 10.1016/S0140-6736(19)33041-7. View

20.

Bur I, Cohen-Solal A, Carmignac D, Abecassis P, Chauvet N, Martin A . The circadian clock components CRY1 and CRY2 are necessary to sustain sex dimorphism in mouse liver metabolism. J Biol Chem. 2009; 284(14):9066-73. PMC: 2666555. DOI: 10.1074/jbc.M808360200. View