Biotechnology and Bioprocess Engineering 2024; 29(5): 845-862  
Chrysin stimulates UCP1-independent thermogenesis in 3T3-L1 adipocytes and mouse model
Jeong Uk Jang1 · Alfin Mohammad Abdillah1 · So Young Bu2 · Jong Won Yun1
1 Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea
2 Department of Food and Nutrition, Daegu University, Gyeongsan 38453, Korea
Correspondence to: ✉ Jong Won Yun
jwyun@daegu.ac.kr
Received: April 14, 2024; Revised: June 16, 2024; Accepted: June 19, 2024; Published online: July 2, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Emerging findings suggest that non-shivering thermogenesis in brown and beige adipocytes may effectively stimulate energy expenditure, thereby contributing to body weight reduction. Our previous report demonstrated that chrysin, a flavone found in honey and propolis, activates uncoupling protein 1 (UCP1)-dependent thermogenesis in brown fat and induces beige adipocytes. However, the effect of chrysin on UCP1-independent thermogenesis remains unexplored. In this study, we examined the effects of chrysin on UCP1-independent thermogenesis in the 3T3-L1 adipocytes and mouse model. This study showed that chrysin elevates the expression of calcium regulatory proteins, including sarcoendoplasmic reticulum Ca2+-ATPase, ryanodine receptor 2, voltage-dependent anion channel, mitochondrial calcium uniporter, and Ca2+/calmodulin-dependent protein kinase 2 in 3T3-L1 adipocytes as well as in inguinal and epididymal white adipose tissues of mice. Furthermore, our results also showed chrysin increased Ca2+ levels in 3T3-L1 adipocytes in a dose-dependent manner. In addition, our study showed chrysin upregulated creatine-mediated thermogenic markers (creatine kinase B and creatine kinase mitochondrial 2) in both in vitro and in vivo models. Mechanistically, we found that chrysin induces UCP1-independent thermogenesis by stimulating creatine- and calcium-mediated ATP-consuming futile cycle through the activation of the α1-adrenergic receptor. Combining the current and previous studies, it can be proposed that chrysin induces both UCP1-dependent and -independent thermogenesis in beige adipocytes, suggesting its possible use for effective intervention for obesity and metabolic disorders.
Keywords: Adipocytes · Chrysin · Obesity · Thermogenesis · Uncoupling protein 1

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