Open AccessThe regulation of HBP1, SIRT1, and SREBP-1c genes and the related microRNAs in non-alcoholic fatty liver rats: The association with the folic acid anti-steatosis
Author(s) -
Muthana S.K. Salman,
Mostafa Kamel,
Sobhy E. Hassab El-Nabi,
Ismail Ahmed,
Sami Ullah,
Ahmed K. Al-Ghamdi,
Heba M. R. Hathout,
Islam El-Garawani
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0265455
Subject(s) - fatty liver , steatosis , medicine , fatty acid synthase , endocrinology , sterol regulatory element binding protein , fatty acid , biology , biochemistry , gene , gene expression , disease
Folic acid is one of the vital micronutrients that contribute to the genetic stability and other biological activities. In addition, microRNAs regulate gene expression through a multittude of pathways. Our current work aimd to explore the possible ameliorative potency of folic acid and its association with the hepatic miR-21, -34a, and -122 expression as well as their targeted genes, HBP1, SIRT1, and SREBP-1c in rats with non-alcoholic fatty liver disease (NAFL). A total of 50 Wistar rats were randomly divided into two groups, a control group (n = 10) and NAFL group (n = 40). Rats in NAFL group were fed a high-fat diet (HFD) containing 20% fats for 14 weeks. The NAFL group was further subdivided into four groups (n = 10/group), one untreated and three orally folic acid-treated groups (25, 50, and 75 μg/Kg b.wt). NAFL characteristics was evaluated in rats in addition to the miR-21, -34a, and -122 profile as well as the transcriptional levels of HBP1, SIRT1, and SREBP-1c genes. NAFL rats exhibited the classic traits of fatty liver disease profile and dysregulation in the pattern of miR-21, -34a, and -122 expression as well as their targeted genes (HBP1, SIRT1, and SREBP-1c, respectively) in the liver. Additionally, NAFL rats had altered levels of TNF-α and adiponectin. These alterations were significantly ameliorated in a dose-dependent pattern following the folic acid treatments. In conclusions, the anti-steatotic, insulin-sensitizing, glucose-lowering and lipotropic potencies of folic acid in NAFL rats may be linked to the epigenetic modulation of the hepatic microRNAs (miR-21, -34a, and -122) and the expression of their target genes (HBP1, SIRT1, and SREBP-1c).