Valerenic Acid Promotes Adipocyte Differentiation, Adiponectin Production, and Glucose Uptake via Its PPARγ Ligand Activity

Jun Takahashi; Nobuyuki Takahashi; Miki Tadaishi; Makoto Shimizu; Kazuo Kobayashi-Hattori

doi:10.1021/acsomega.2c06120

Valerenic Acid Promotes Adipocyte Differentiation, Adiponectin Production, and Glucose Uptake via Its PPARγ Ligand Activity

ACS Omega. 2022 Dec 13;7(51):48113-48120. doi: 10.1021/acsomega.2c06120. eCollection 2022 Dec 27.

Authors

Jun Takahashi¹, Nobuyuki Takahashi², Miki Tadaishi¹, Makoto Shimizu¹, Kazuo Kobayashi-Hattori¹

Affiliations

¹ Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
² Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.

Abstract

Although valerenic acid (VA) is an important marker compound for quantitative assessment of Valeriana officinalis products, little is known about its potential effects on adipocytes. We investigated the effects of VA on adipocyte differentiation, adiponectin production, and glucose uptake using 3T3-L1 adipocytes. The results showed that VA promoted adipocyte differentiation and increased the gene expression of adipogenesis and glucose uptake-related proteins, including peroxisome proliferator-activated receptor gamma (PPARγ), cytosine-cytosine-adenosine-adenosine-thymidine enhancer binding protein alpha (C/EBPα), adiponectin, and glucose transporter 4 (GLUT4). Additionally, cell cultures treated with VA had elevated adiponectin secretion and glucose uptake. The PPARγ luciferase assay indicated VA as a partial agonist of PPARγ, while the analysis using its antagonist, GW9662, and a docking simulation between PPARγ and VA revealed the binding site of VA as likely adjacent to the Ω loop pocket of PPARγ. Taken together, these results demonstrate that VA acts as a PPARγ partial agonist to promote adipocyte differentiation, adiponectin production, and glucose uptake.