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Phytosteroid 28-homobrassinolide targets cholesterol and glucose homeostasis implicating ABCA1 and SREBP role in regulation.

Authors
  • Mukherjee, Victor1
  • Ramakrishna, Premalatha2
  • Bora, Sushmita3
  • Kotteazeth, Srikumar4
  • 1 Department of Biochemistry & Molecular Biology, School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India; Interdisciplinary Program in Life Sciences (DBT-BUILDER) School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India. , (India)
  • 2 Division of Biosciences, Pondicherry University Community College, Lawspet, Pondicherry 605008, India. , (India)
  • 3 Department of Biochemistry & Molecular Biology, School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India. , (India)
  • 4 Department of Biochemistry & Molecular Biology, School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Steroids
Publication Date
Nov 07, 2020
Volume
165
Pages
108756–108756
Identifiers
DOI: 10.1016/j.steroids.2020.108756
PMID: 33171131
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Oxysterols are natural ligands of certain nuclear receptors known as liver X receptors (LXR). LXRs are regulators of fatty acid, cholesterol, and glucose homeostasis. Dietary phyto-oxysterol 28-homobrassinolide (28-HB) has been demonstrated to transactivate rat LXR α and β. In this study we assessed the potential of 28-HB to effect such changes in - (1) human HepG2 cancer cell line, (2) isolated perfused goat liver, and (3) high-fat diet-fed C57BL/6J mice. Serum and perfusate marker levels along with hexokinase activity were determined through enzyme assays. Fat deposition was studied by Oil Red O staining, ATP-binding cassette transporter (ABCA1), and sterol regulatory element-binding transcription factor 2 (SREBP2) protein expression by Western blot and their mRNA expression through real-time PCR. In HepG2 cells, 28-HB (5-20 μM) treatment indicated a 2-fold increase in glucose utilization and ABCA1 and SREBP2 protein expression within 12 h. Tissue glucose and cholesterol levels decreased in 28-HB perfused goat liver within 2 h, whereas cholesterol level increased 54% in the perfusate (p < 0.05) and tissue hexokinase activity increased 23% (p < 0.05). Glucokinase, ABCA1, and SREBF1 gene expression increased 2.6, 5.37, and 2.85 fold respectively in the perfused tissue after 4 h. High-fat diet-fed C57BL/6J mice when treated with 28-HB (1-20 µg/day) for 6 weeks exhibited a marked decrease in aortic fat deposit and serum marker levels. Our study suggests that 28-HB modulates cholesterol and glucose homeostasis in animal cells through activation of LXR involving ABCA1 and SREBP-1 and 2 augmentations. Copyright © 2020 Elsevier Inc. All rights reserved.

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