Association between hepatocyte TM4SF5 expression and gut microbiome dysbiosis during non-alcoholic fatty liver disease development.

Autor: Pinanga YD; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Pyo KH; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Shin EA; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Lee H; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Lee EH; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Kim W; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Kim S; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Kim JE; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Kim S; Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejon 34141, Republic of Korea., Lee JW; Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: jwl@snu.ac.kr.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Dec 01; Vol. 358, pp. 123164. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1016/j.lfs.2024.123164
Abstrakt: Gut microbiome dysbiosis is involved in non-alcoholic fatty liver disease (NAFLD) development. Hepatic transmembrane 4 L six family member 5 (TM4SF5) overexpression promotes NAFLD. However, how gut microbiota are associated with TM4SF5-mediated NAFLD remains unexplored. We analyzed the gut microbiome using feces from hepatocyte-specific TM4SF5-overexpressing transgenic (Alb-TG Tm4sf5 -Flag , TG) or Tm4sf5 -/- knock-out (KO) mice fed a normal chow diet (NCD), high-fat diet (HFD) for 2 weeks (HFD 2W ), or methionine-choline-deficient diet (MCD) for 4 weeks to investigate associations among Tm4sf5 expression, diet, and the gut microbiome. TG-NCD mice showed a higher Firmicutes-to-Bacteroidetes (F/B) ratio, with less enrichment of Akkermansia muciniphila and Lactobacillus reuteri. NASH-related microbiomes in feces were more abundant in TG-HFD 2w mice than in KO-HFD 2w mice. Further, TG-MCD showed a higher F/B ratio than TG-NCD or KO mice, with decreases or increases in microbiomes beneficial or detrimental to the liver, respectively. Such effects in TG-MCD animals were correlated with functional pathways producing short-chain fatty acids (SCFAs). Furthermore, potential functional pathways of the gut microbiome were metabolically parallel to NAFLD features in TG-MCD mice. These results suggest that hepatocyte Tm4sf5 supports gut microbiome dysbiosis and metabolic activity, leading to SCFA production and hepatic inflammation during NAFLD development.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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