Protective effects of 5-heptadecylresorcinol against adipocyte mitochondrial dysfunction through upregulation of Sirt3-me diate d autophagy

5-heptadecylresorcinol (AR-C17), a natural phenolic lipid component and biomarker of whole grain rye consumption, has been widely reported to confer multiple health benefits. However, the molecular mechanism underlying its potential protective effect against obesity and other related diseases is still unclear. In the present study, we investigated the potential role and mechanism of AR-C17 in mitigating mitochondrial dysfunction and lipid disturbance of adipocytes both in vitro and in vivo. AR-C17 treatment alleviated inflammatory conditioned medium (CM) induced adipocyte lipolysis and mitochondrial damage, accompanied by attenuated mitochondrial reactive oxygen species production and mitochondrial membrane depolarization. Moreover, we observed improved mitochondrial content, upregulated expression of mitochondrial biogenesis related transcription factors and increased oxygen consumption rate. Meanwhile, AR-C17 attenuated CM-mediated adipocyte mitochondria dysfunction by promoting autophagy, followed by the enhancement of autophagic flux and related protein expression, such as LC3B-II/I, Beclin1, Atg5, PINK1 and Parkin. Further analysis showed that the protective effect of AR-C17 against mitochondrial dysfunction was depended on the upregulation of Sirt3-mediated autophagy. At the whole animal level, AR-C17 administration ameliorated high-fat diet induced C57BL/6J mice obesity and its associated adipose tissue macrophage infiltration and mitochondrial dysfunction. Activation of Sirt3mediated autophagy in adipose tissue was also observed in AR-C17-treated mice. Together, these findings indicate that Sirt3-mediated autophagy plays an essential role in alleviating adipocyte mitochondrial dysfunction by AR-C17 and suggest AR-C17 as a potential dietary bioactive ingredient for obesity prevention and treatment. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study investigates the potential role and mechanism of 5-heptadecylresorcinol (AR-C17) in mitigating mitochondrial dysfunction and lipid disturbance in adipocytes. The results suggest that AR-C17 treatment can alleviate adipocyte lipolysis, mitochondrial damage, and oxidative stress. Furthermore, AR-C17 promotes autophagy and enhances mitochondrial biogenesis, leading to improved adipocyte mitochondrial function. In a mouse model, AR-C17 administration ameliorates obesity and adipose tissue inflammation, with activation of Sirt3-mediated autophagy observed. These findings highlight the potential of AR-C17 as a dietary bioactive ingredient for obesity prevention and treatment.