Farnesol induces mitochondrial/peroxisomal biogenesis and thermogenesis by enhancing the AMPK signaling pathway in vivo and in vitro

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 7 coactivator 1 alpha (PGC1 alpha), and PR domain zinc-finger protein 16 (PRDM16) together with the phosphorylation of AMP-activated protein kinase alpha (AMPK alpha) 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 (3-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 AMPKa activation using Compound C inhibitor or siRNA-AMPK alpha knockdown. These results suggest that farnesol may be a potential agent for the treatment of obesity by inducing energy consumption through heat generation.

Automated summary

This study demonstrates that farnesol induces thermogenesis in brown adipose tissue by activating AMP-activated protein kinase alpha, promoting lipolytic enzyme activity, and increasing expression of oxidative phosphorylation complexes and peroxisomes. These findings suggest that farnesol may be a potential treatment for obesity by promoting energy consumption through heat generation.