Saijou Eiko, Kamiya Yoshiko, Fujiki Katsunori, Shirahige Katsuhiko, Nakato Ryuichiro
Laboratory of Computational Genomics, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
Heliyon. 2024 Aug 31;10(17):e36727. doi: 10.1016/j.heliyon.2024.e36727. eCollection 2024 Sep 15.
Liver fibrosis is a critical global health challenge, often leading to severe liver diseases without timely intervention. Choline deficiency has been linked to metabolic dysfunction associated steatohepatitis (MASH) and liver fibrosis, suggesting choline supplementation as a potential therapeutic approach. This study aimed to explore the therapeutic potential of choline supplementation in liver fibrosis resolution and its effects on cholesterol homeostasis using a mouse model with induced liver fibrosis. Our findings reveal that choline supplementation significantly decreases blood lactate dehydrogenase (LDH) and non-high-density lipoprotein cholesterol (non-HDL-C) levels. Transcriptome analysis showed that choline supplementation primarily induces genes related to cholesterol homeostasis, suggesting a significant impact on liver cholesterol synthesis. However, choline supplementation did not significantly alter the expression of fibrosis-related, choline metabolism-related, or epigenetics-related genes. This study provides novel insights into the role of choline in liver health and cholesterol metabolism, potentially informing treatments for liver fibrosis and related conditions.
肝纤维化是一项严峻的全球健康挑战，若不及时干预，常常会导致严重的肝脏疾病。胆碱缺乏与代谢功能障碍相关脂肪性肝炎（MASH）及肝纤维化有关，这表明补充胆碱是一种潜在的治疗方法。本研究旨在利用诱导性肝纤维化小鼠模型，探索补充胆碱在肝纤维化消退中的治疗潜力及其对胆固醇稳态的影响。我们的研究结果显示，补充胆碱可显著降低血液乳酸脱氢酶（LDH）和非高密度脂蛋白胆固醇（non-HDL-C）水平。转录组分析表明，补充胆碱主要诱导与胆固醇稳态相关的基因，提示对肝脏胆固醇合成有显著影响。然而，补充胆碱并未显著改变纤维化相关、胆碱代谢相关或表观遗传学相关基因的表达。本研究为胆碱在肝脏健康和胆固醇代谢中的作用提供了新的见解，可能为肝纤维化及相关病症的治疗提供依据。
