Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”

Article information

Clin Mol Hepatol. 2025;31(2):e226-e227

Publication date (electronic) : 2025 February 13

doi : https://doi.org/10.3350/cmh.2025.0128

Yoon-su Ha ¹, Won Kim^,²

, Seung-Jin Kim^,¹

¹Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Korea

²Department of Internal Medicine, Division of Gastroenterology and Hepatology Seoul National University College of Medicine Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

Corresponding author : Seung-Jin Kim Department of Biochemistry, College of Natural Sciences, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon 24341, Korea Tel: +82-33-250-8515, Fax: +82-33-259-5748, E-mail: sjk@kangwon.ac.kr

Won Kim Department of Internal Medicine, Division of Gastroenterology and Hepatology Seoul National University College of Medicine Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Tel: +82-2-870-2233, Fax: +82-2-831-2826, E-mail: drwon1@snu.ac.kr

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

Received 2025 February 4; Accepted 2025 February 12.

See the Original "Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”" on page e186.

Keywords: Metabolic dysfunction-associated steatohepatitis; Golgi membrane protein 1; Cholesterol metabolism; ATP-binding cassette subfamily G member 5

Dear Editor,

The recent publication of “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” in Clinical and Molecular Hepatology provides valuable insights into the molecular mechanisms underlying cholesterol gallstone (CGS) formation in metabolic dysfunction-associated steatohepatitis (MASH) [1]. In response, we authored the editorial “Unraveling the role of GOLM1-OPN-ABCG5 axis in MASH” [2]. Drs. Yi-Tong Li, WeiQing Shao, Zhen-Mei Chen, Jing Lin, and Jin-Hong Chen subsequently provided a detailed response to our editorial [3]. We appreciate their comprehensive discussion and response to the points raised in our editorial; we look forward to further constructive discourse regarding their findings.

The identification of molecular targets in MASH remains a critical issue within biomedical research [4-7]. Li et al. provided a very interesting discussion offering significant understanding of the mechanistic relationship between MASH and the formation of CGS [1]. As emphasized in their correspondence, sex-related factors, particularly estrogen, may influence the development of MASH and CGS [3]. We agree that further investigation into the precise role of estrogen in MASH-related CGS formation is essential for a more comprehensive understanding of the underlying mechanisms. Several studies have demonstrated the influence of estrogen on gallstone formation, highlighting the involvement of estrogen receptor GPR30 in promoting additional lithogenic effects. This receptor functions independently of ERα, thereby facilitating cholesterol cholelithogenesis in female mice [8-10]. Considering the complexity of these interactions, we expect that future studies concerning the impact of sexrelated factors on MASH pathophysiology will provide valuable insights, contributing to the development of more effective and sex-specific therapeutic strategies. We also agree with the authors’ assertion that a tissue-specific knockout system (e.g., liver, adipose tissue) would effectively address a key research gap, particularly given the relationship between MASH livers and Golgi membrane protein 1 (GOLM1) expression levels. A previous study by Shen et al. [11] revealed elevated serum GOLM1 levels in patients with osteoporosis and increased GOLM1 expression in bone marrow mesenchymal stem cells (i.e., progenitors of adipocytes, chondrocytes, and osteoblasts) in an ovariectomy-induced osteoporosis mouse model. These findings suggest that GOLM1 is involved in various pathophysiological processes; further studies are warranted to investigate its potential as a therapeutic target in these conditions.

In summary, increasing evidence links GOLM1 to multiple pathophysiological processes, underscoring its potential as both a biomarker and a therapeutic target. Further investigation of GOLM1 is expected to enhance its clinical applicability and improve disease management and treatment outcomes for patients with MASH.

Notes

Authors’ contribution

YSH designed and wrote the manuscript; WK and SJK supervised the whole project and wrote the manuscript.

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2022R1C1C1002819).

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

CGS

cholesterol gallstone

GOLM1

Golgi membrane protein 1

MASH

metabolic dysfunction-associated steatohepatitis

References

1. Li YT, Shao WQ, Chen ZM, Ma XC, Yi CH, Tao BR, et al. GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers. Clin Mol Hepatol 2025;31:409–425.

2. Ha YS, Kim W, Kim SJ. Unraveling the role of GOLM1-OPNABCG5 axis in MASH: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”. Clin Mol Hepatol 2025;31:628–630.

3. Li YT, Shao WQ, Chen ZM, Lin J, Chen JH. Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”. Clin Mol Hepatol 2025;31:e186–e188.

4. Parker R, Kim SJ, Gao B. Alcohol, adipose tissue and liver disease: mechanistic links and clinical considerations. Nat Rev Gastroenterol Hepatol 2018;15:50–59.

5. Kim SJ, Feng D, Guillot A, Dai S, Liu F, Hwang S, et al. Adipocyte death preferentially induces liver injury and inflammation through the activation of chemokine (C-C motif) receptor 2-positive macrophages and lipolysis. Hepatology 2019;69:1965–1982.

6. Kim GA, Moon JH, Kim W. Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity. Clin Mol Hepatol 2023;29:831–843.

7. Yoo JJ, Kim W, Kim MY, Jun DW, Kim SG, Yeon JE, et al. Recent research trends and updates on nonalcoholic fatty liver disease. Clin Mol Hepatol 2019;25:1–11.

8. Wang HH, Afdhal NH, Wang DQ. Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones. Gastroenterology 2004;127:239–249.

9. Wang HH, de Bari O, Arnatt CK, Liu M, Portincasa P, Wang DQ. Activation of estrogen receptor G protein-coupled receptor 30 enhances cholesterol cholelithogenesis in female mice. Hepatology 2020;72:2077–2089.

10. Radmard AR, Merat S, Kooraki S, Ashraf M, Keshtkar A, Sharafkhah M, et al. Gallstone disease and obesity: a population-based study on abdominal fat distribution and gender differences. Ann Hepatol 2015;14:702–709.

11. Shen G, Zhang H, Jia P, Li G, Wang X, Zhou X, et al. GOLM1 stimulation of glutamine metabolism promotes osteoporosis via inhibiting osteogenic differentiation of BMSCs. Cell Physiol Biochem 2018;50:1916–1928.

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