Icariin Improves Lipid Metabolism via PGC1-α/FNDC5/UCP1 Pathway

Abstract

Recently, more and more studies have confirmed that icariin prevent diet-induced obesity and insulin resistance to improve lipid metabolism. FNDC5/Irisin also elicit anti-obesity effects by inducing browning of white adipose tissue(WAT) stimulating uncoupling protein 1(UCP1) expression. In female FNDC5 knockout(FNDC5-KO) mice, we found that FNDC5 deficiency worsened the age-induced obesity. Therefore, The purpose of this study was to investigate the therapeutic effect and mechanism of icariin in middle-aged mice with FNDC5 knockout-induced obesity. FNDC5-KO mice were used to determine the roles of FNDC5 in lipid metabolism by qPCR, H&E and their body weights and serum cholesterol(TC), triglyceride(TG) were detected. The therapeutic efficacy of icariin on lipid metabolism were further investigated in icariin-treated mice aged 50-52weeks. FNDC5-KO reduced the browning of WAT and worsened the age-induced fat accumulation and weight gain only in female mice. Icariin ruduced body weight and increased FNDC5, PGC1-α, and UCP1 expression levels in WAT, suggesting that icariin improves lipid metabolism via the PGC1-α/FNDC5/UCP1 pathway, but the effect was blocked by FNDC5-KO only in female. Taken together, icariin effectively reduce body weight and adipose content by promoting the browning of WAT via the PGC1-α/FNDC5/UCP1 pathway. FNDC5 is essential for the effect of icariin only in female mice, indicating the sex differences of icariin are accounted for the differences on FNDC5. Funding: This study was funded by the project of the Natural Science Foundation of Guangdong Province (2018A030313632); the project of the Traditional Chinese Medicine Bureau of Guangdong Province (20211118) to Fuping Ding. Declaration of Interest: None to declare. Ethical Approval: All experimental procedures were performed in accordance with the Guidelines of Animal Experiments from the Committee of Medical Ethics, National Health Department of China. Animal experiments were approved by the Animal Research Center of Guangzhou University of Chinese Medicine. All efforts were made to reduce animal discomfort and the number of animals used.