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Review
. 2024 Dec 30:12:goae108.
doi: 10.1093/gastro/goae108. eCollection 2024.

The effect and application of adiponectin in hepatic fibrosis

Taoran Chen  1 , Wenjing Yang  1 , Rongrong Dong  1 , Han Yao  1 , Miao Sun  1 , Jiaxin Wang  1 , Qi Zhou  2 , Jiancheng Xu  1
Affiliations
Review

The effect and application of adiponectin in hepatic fibrosis

Taoran Chen et al. Gastroenterol Rep (Oxf). .

Abstract

Hepatic fibrosis, a degenerative liver lesion, significantly contributes to the deterioration and mortality among patients with chronic liver diseases. The condition arises from various factors including toxins, such as alcohol, infections like different types of viral hepatitis, and metabolic diseases. Currently, there are no effective treatments available for liver fibrosis. Recent research has shown that adiponectin (ADPN) exhibits inhibitory effects on hepatic fibrosis. ADPN, an adipocytokine secreted by mature adipocytes, features receptors that are widely distributed across multiple tissues, especially the liver. In the liver, direct effects of ADPN on liver fibrosis include reducing inflammation and regulating hepatic stellate cell proliferation and migration. And its indirect effects include alleviating hepatic endoplasmic reticulum stress and reducing inflammation in hepatic lobules, thereby mitigating hepatic fibrosis. This review aims to elucidate the regulatory role of ADPN in liver fibrosis, explore how ADPN and its receptors alleviate endoplasmic reticulum stress, summarize ADPN detection methods, and discuss its potential as a novel marker and therapeutic agent in combating hepatic fibrosis.

Keywords: adiponectin; cirrhosis; endoplasmic reticulum stress; hepatic fibrosis; hepatic stellate cell.

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Conflict of interest statement

The authors have indicated they have no potential conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
The process of HSC development. The figure showed that hepatocyte injury triggers an inflammatory response that releases ROS and transforming growth factor β1 (TGFβ-1) and activates qHSC-aHSC myofibroblasts. aHSC/myofibroblasts proliferate in response to a variety of cytokines (PDGF), secrete type I collagen, and fibrogenize the liver. One key feature of qHSC is the expression of vitamin A, which is gradually down-regulated during the transition to aHSC and restored after aHSC inactivation. HSC = hepatic stellate cells, ROS = reactive oxygen species, TGFβ-1 = transforming growth factor β1, qHSC = quiescent HSCs, aHSC = activated form of HSCs.
Figure 2.
Figure 2.
The structure of ADPN. Adiponectin exists as a full-length plasma protein of 30 kDa, circulating in serum as three major isoforms: trimer, hexamer, and high-molecular-weight multimer. Extravasation of ADPN from circulation to target tissues. ADPN = adiponectin.
Figure 3.
Figure 3.
Mechanisms of endoplasmic reticulum stress initiation. The accumulation of unfolded proteins results in the release of GRP78, which activates PERK, IRE1-α, and ATF6. These proteins activate transcription and inhibit translation. GRP78 = glucose-regulated protein 78, PERK = PKR-like endoplasmic reticulum kinase, IRE1-α = inositol-requiring enzyme 1-α, ATF6 = activating transcription factor 6.
Figure 4.
Figure 4.
Mechanisms of ADPN to alleviate ERS and hepatic fibrosis. Relationship between downstream signaling of the ADPN and ERS. The red-labeled portion of the figure illustrates the principal pathway of action of ADPN on hepatic fibrosis. ADPN = adiponectin, ERS = endoplasmic reticulum stress.
Figure 5.
Figure 5.
ADPN clinical therapies. A mechanistic sketch of ADPN in combination therapy with anti-insulin resistance drugs. ADPN = adiponectin.
See this image and copyright information in PMC

References

    1. Devarbhavi H, Asrani SK, Arab JP. et al. Global burden of liver disease: 2023 update. J Hepatol 2023;79:516–37. - PubMed
    1. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020;5:245–66. - PMC - PubMed
    1. Zhao Q, Liang L, Zhai F. et al. A bibliometric and visualized analysis of liver fibrosis from 2002 to 2022. J Gastroenterol Hepatol 2023;38:359–69. - PubMed
    1. Rowe IA. Lessons from epidemiology: the burden of liver disease. Dig Dis 2017;35:304–9. - PubMed
    1. She H, Xiong S, Hazra S. et al. Adipogenic transcriptional regulation of hepatic stellate cells. J Biol Chem 2005;280:4959–67. - PubMed

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