Farnesol induces mitochondrial/peroxisomal biogenesis and thermogenesis by enhancing the AMPK signaling pathway in vivo and in vitro. (January 2021)

• Record Type: Journal Article
• Authors: Cho, Seon Yeon; Lim, Seona; Ahn, Kwang Seok; Kwak, Hyun Jeong; Park, Jinbong; Um, Jae-Young
• Is Part Of: Pharmacological research. Volume 163(2021)
• Publication Date: 2021-01
• Subjects: PEX13 peroxisomal biogenesis factor 13 -- TOM20 translocase of the outer membrane 20 -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- PRDM16 PR domain zinc-finger protein 16 -- CPT1β carnitine palmitoyltransferase 1 beta -- ACOX1 peroxisomal acyl-coenzyme A oxidase 1 -- PPARα peroxisome proliferator-activated receptor alpha -- PPARγ peroxisome proliferator-activated receptor gamma -- PMP70 70-kDa peroxisomal membrane protein -- PGC1α peroxisome proliferator-activated receptor gamma coactivator 1 alpha -- HSL hormone sensitive lipase -- ATGL adipose triglyceride lipase -- OXPHOS oxidative phosphorylation -- UCP1 uncoupling protein 1 -- NRF1 nuclear respiratory factor 1 -- AMPKα AMP-activated protein kinase alpha -- LKB liver kinase B1 -- ACC acetyl-CoA carboxylase -- FXR farnesoid X receptor -- CytC cytochrome c -- PDK4 Pyruvate Dehydrogenase Kinase 4 -- HDL high-density lipoprotein -- LDL low-density lipoprotein -- BAT brown adipose tissue -- ND normal-diet -- HFD high-fat-diet -- DM (Br) brown adipocytes differentiation media; Farnesol -- PubChem CID: 445070; Farnesol -- Thermogenesis -- Mitochondria -- Peroxisome -- AMPKα; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105312
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Thermogenic activation of brown adipose tissue has been considered as an obesity treatment strategy that consumes energy. In this study, we investigated whether farnesol in vivo and in vitro models induces thermogenesis and affect the activation of the mitochondria and peroxisomes, which are key organelles in activated brown adipocytes. Farnesol induced the expression of thermogenic factors such as uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1α), and PR domain zinc-finger protein 16 (PRDM16) together with the phosphorylation of AMP-activated protein kinase alpha (AMPKα) in brown adipose tissue and primary cultured brown adipocytes. Farnesol promoted lipolytic enzymes: hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). We confirmed that these inductions of lipolysis by farnesol were the underlying causes of β-oxidation activation. Farnesol also increased the expression of oxidative phosphorylation (OXPHOS) complexes and the oxygen consumption rate (OCR) and the expansion of peroxisomes. Moreover, we proved that the thermogenic activity of farnesol was dependent on AMPKα activation using Compound C inhibitor or siRNA-AMPKα knockdown. These results suggest that farnesol may be a potential agent for the treatment of obesity by inducing energy consumption through heat generation.