한빛사논문
- 조회415
Dong Yun Kim 1,2,3, Jun Yong Park 2,3,* and Heon Yung Gee 1,4,5,*
1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of South Korea.
2Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of South Korea.
3Yonsei Liver Center, Severance Hospital, Seoul, Republic of South Korea.
4Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of South Korea.
5Woo Choo Lee Institute for Precision Drug Development, Seoul, Republic of South Korea.
*Corresponding authors: correspondence to Jun Yong Park or Heon Yung Gee
Abstract
Lactobacillus is a probiotic with therapeutic potential for several diseases, including liver disease. However, the therapeutic effect of L. plantarum against nonalcoholic steatohepatitis (NASH) and its underlying mechanisms remain unelucidated. Therefore, we delineated the L. plantarum-mediated NASH regulation in a mouse model to understand its therapeutic effect. We used a choline-deficient high-fat diet (CD-HFD)-induced murine model that recapitulated the critical features of human metabolic syndrome and investigated the effect of L. plantarum on NASH pathogenesis using transcriptomic, metagenomic, and immunohistochemistry analyses. Validation experiments were performed using liver organoids and a murine model fed a methionine-choline-deficient (MCD) diet. L. plantarum treatment in mice significantly decreased liver inflammation and improved metabolic phenotypes, such as insulin tolerance and the hepatic lipid content, compared with those in the vehicle group. RNA-sequencing analysis revealed that L. plantarum treatment significantly downregulated inflammation-related pathways. Shotgun metagenomic analysis revealed that L-arginine biosynthesis-related microbial genes were significantly upregulated in the L. plantarum group. We also confirmed the elevated arginine levels in the serum of the L. plantarum group. We further used liver organoids and mice fed an MCD diet to demonstrate that L-arginine alone was sufficient to alleviate liver inflammation. Our data revealed a novel and counterintuitive therapeutic effect of L. plantarum on alleviating NASH-related liver inflammation by increasing circulating L-arginine.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-01)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
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