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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Naphthofuran Derivative BF4, a New Potent SIRT1 Activator, Regulates Lipid Metabolism in 3T3-L1 Adipocytes via the SIRT1-AMPK Pathway

Author(s): Jian Gao, Fan Li, Ye Huang, Shihao Li and Qisi Lin*

Volume 19, Issue 9, 2023

Published on: 28 April, 2023

Page: [879 - 888] Pages: 10

DOI: 10.2174/1573406419666230330141501

Price: $65

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Abstract

Aim: Our previously reported naphthofuran derivative BF4, identified as a potent silent information regulator 1 (SIRT1) activator, could alleviate high glucose stimulating apoptosis and inflammation response in human renal tubular epithelial (HK-2) cells.

Introduction: In this study, the underlying effects of BF4 on lipid metabolism in 3T3-L1 adipocytes were investigated.

Methods: The effects of BF4 on pre-adipocyte differentiation and adipocyte lipolysis were studied using oil red O staining and quantitative glycerol and triglyceride content assay kits. Moreover, the molecular mechanism of BF4 on adipogenesis and lipid metabolism in 3T3-L1 adipocytes was investigated by real-time quantitative PCR and Western blotting analysis.

Results: We found that compound BF4 significantly decreased adipogenesis and lipid accumulation and inhibited the differentiation of 3T3-L1 pre-adipocytes into adipocytes. Moreover, compound BF4 decreased the expressions of several key regulators in adipocyte differentiation, including C/EBPβ and PPARγ, and their downstream lipogenesis targets via the activation of the SIRT1/ AMPK pathway.

Conclusion: Our results demonstrated that the novel SIRT1 activator BF4 might be a potent candidate for regulating lipid metabolism.

Keywords: Obesity, SIRT1 activator, BF4, lipid metabolism, SIRT1/AMPK pathway, C/EBPβ, PPARγ.

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