The Potential Role of C-Reactive Protein in Metabolic-Dysfunction-Associated Fatty Liver Disease and Aging

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2023 Oct 28

PMID 37893085

Authors

Zheng Ding

Yuqiu Wei

Jing Peng

Siyu Wang

Guixi Chen

Jiazeng Sun

Affiliations

Soon will be listed here.

Abstract

Nonalcoholic fatty liver disease (NAFLD), recently redefined as metabolic-dysfunction-associated fatty liver disease (MASLD), is liver-metabolism-associated steatohepatitis caused by nonalcoholic factors. NAFLD/MASLD is currently the most prevalent liver disease in the world, affecting one-fourth of the global population, and its prevalence increases with age. Current treatments are limited; one important reason hindering drug development is the insufficient understanding of the onset and pathogenesis of NAFLD/MASLD. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. As a conserved acute-phase protein, CRP is widely characterized for its host defense functions, but the link between CRP and NAFLD/MASLD remains unclear. Herein, we discuss the currently available evidence for the involvement of CRP in MASLD to identify areas where further research is needed. We hope this review can provide new insights into the development of aging-associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

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References

Mattecka S, Brunner P, Hahnel B, Kunze R, Vogt B, Sheriff A . PentraSorb C-Reactive Protein: Characterization of the Selective C-Reactive Protein Adsorber Resin. Ther Apher Dial. 2019; 23(5):474-481. DOI: 10.1111/1744-9987.12796. View

Kumar R, Porwal Y, Dev N, Kumar P, Chakravarthy S, Kumawat A . Association of high-sensitivity C-reactive protein (hs-CRP) with non-alcoholic fatty liver disease (NAFLD) in Asian Indians: A cross-sectional study. J Family Med Prim Care. 2020; 9(1):390-394. PMC: 7014887. DOI: 10.4103/jfmpc.jfmpc_887_19. View

Ryu J, Jung I, Park E, Kim K, Kim K, Yeom J . Radiation-induced C-reactive protein triggers apoptosis of vascular smooth muscle cells through ROS interfering with the STAT3/Ref-1 complex. J Cell Mol Med. 2022; 26(7):2104-2118. PMC: 8980952. DOI: 10.1111/jcmm.17233. View

Yeh E, Willerson J . Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation. 2003; 107(3):370-1. DOI: 10.1161/01.cir.0000053731.05365.5a. View

Noureddin M, Yates K, Vaughn I, Neuschwander-Tetri B, Sanyal A, McCullough A . Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology. 2013; 58(5):1644-54. PMC: 3760979. DOI: 10.1002/hep.26465. View

Szalai A, McCrory M, Xing D, Hage F, Miller A, Oparil S . Inhibiting C-reactive protein for the treatment of cardiovascular disease: promising evidence from rodent models. Mediators Inflamm. 2014; 2014:353614. PMC: 3996300. DOI: 10.1155/2014/353614. View

Fang C, Pan J, Qu N, Lei Y, Han J, Zhang J . The AMPK pathway in fatty liver disease. Front Physiol. 2022; 13:970292. PMC: 9531345. DOI: 10.3389/fphys.2022.970292. View

Polyzos S, Kountouras J, Mantzoros C . Leptin in nonalcoholic fatty liver disease: a narrative review. Metabolism. 2014; 64(1):60-78. DOI: 10.1016/j.metabol.2014.10.012. View

Shamsuzzaman A, Winnicki M, Wolk R, Svatikova A, Phillips B, Davison D . Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation. 2004; 109(18):2181-5. DOI: 10.1161/01.CIR.0000127960.28627.75. View

10.

Perumpail B, Li A, John N, Sallam S, Shah N, Kwong W . The Role of Vitamin E in the Treatment of NAFLD. Diseases. 2018; 6(4). PMC: 6313719. DOI: 10.3390/diseases6040086. View

11.

Esposito F, Matthes H, Schad F . Seven COVID-19 Patients Treated with C-Reactive Protein (CRP) Apheresis. J Clin Med. 2022; 11(7). PMC: 8999883. DOI: 10.3390/jcm11071956. View

12.

Schulze R, Schott M, Casey C, Tuma P, McNiven M . The cell biology of the hepatocyte: A membrane trafficking machine. J Cell Biol. 2019; 218(7):2096-2112. PMC: 6605791. DOI: 10.1083/jcb.201903090. View

13.

Agrawal A, Samols D, Kushner I . Transactivation of C-reactive protein by IL-6 requires synergistic interaction of CCAAT/enhancer binding protein beta (C/EBP beta) and Rel p50. J Immunol. 2001; 166(4):2378-84. DOI: 10.4049/jimmunol.166.4.2378. View

14.

Forte L, Cimmino G, Loffredo F, De Palma R, Abbate G, Calabro P . C-reactive protein is released in the coronary circulation and causes endothelial dysfunction in patients with acute coronary syndromes. Int J Cardiol. 2011; 152(1):7-12. DOI: 10.1016/j.ijcard.2011.05.062. View

15.

Zhao Y, Yang Y, Li Q, Li J . Understanding the Unique Microenvironment in the Aging Liver. Front Med (Lausanne). 2022; 9:842024. PMC: 8907916. DOI: 10.3389/fmed.2022.842024. View

16.

Chen Z, Nilsson E, Lindholm B, Heimburger O, Barany P, Stenvinkel P . Low-Plasma Insulin-Like Growth Factor-1 Associates With Increased Mortality in Chronic Kidney Disease Patients With Reduced Muscle Strength. J Ren Nutr. 2022; 33(2):298-306. DOI: 10.1053/j.jrn.2022.06.008. View

17.

Macintyre S, Samols D, Dailey P . Two carboxylesterases bind C-reactive protein within the endoplasmic reticulum and regulate its secretion during the acute phase response. J Biol Chem. 1994; 269(39):24496-503. View

18.

Liss K, Finck B . PPARs and nonalcoholic fatty liver disease. Biochimie. 2016; 136:65-74. PMC: 5380579. DOI: 10.1016/j.biochi.2016.11.009. View

19.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

20.

Stanley T, Fourman L, Zheng I, McClure C, Feldpausch M, Torriani M . Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab. 2020; 106(2):e520-e533. PMC: 7823253. DOI: 10.1210/clinem/dgaa792. View