title: Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway.
abstract: Irisin, derived from FNDC5, is an exercise-induced myokine that can stimulate the 'browning' of white adipose tissue, which is regulated by peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α). Dihydromyricetin (DHM), a natural flavonoid, exerts its activities through PGC-1α activation. Here, we explored whether DHM could mimic the effects of exercise on irisin secretion. DHM administration increased circulating irisin in rats and humans. Notably, the serum irisin level had a greater correlation to the level of circulating DHM than to the amount of exercise. DHM treatment upregulated PGC-1α and FNDC5 expression, enhanced energy metabolism, as evidenced by NMR-based metabonomics analysis, and partially abolished the suppressive effects of Pgc-1α siRNA on FNDC5 expression. These results suggest that DHM can stimulate irisin secretion partially via the PGC-1α pathway. As a potent exercise mimetic, DHM is expected to benefit patients suffering from metabolic diseases, especially those who cannot undergo rigorous exercise.
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ka
authors.initials: K
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zou
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Deng
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qianyong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: mimantian@sina.com.
authors.forename: Mantian
authors.initials: M
authors.lastname: Mi
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D002478:Cells, Cultured; D005353:Fibronectins / Q000097:blood / Q000378:metabolism*; D044948:Flavonols / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000963:Antimetabolites; C583676:FNDC5 protein, rat; D005353:Fibronectins; D044948:Flavonols; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; C472036:dihydromyricetin
keywords: Dihydromyricetin (DHM); FNDC5; Irisin; Myokine; PGC-1α