Abstract
Objectives
Cafestol, a diterpene found in coffee beans, is reported to be an agonist of farnesoid X receptors (FXR), nuclear hormone receptors involved in cholesterol homeostasis. It is also known that FXR plays critical roles in other metabolic pathways, including lipid metabolism; however, little is known about cafestol's effects on lipid metabolism. The goal of the current study was to investigate the effects of cafestol on lipid metabolism using Caenorhabditis elegans as a model system.
Methods
C. elegans was treated for 2 days with cafestol or 0.2% dimethyl sulfoxide (vehicle control). Triglycerides, locomotor behavior (an indicator of energy expenditure) and lipid metabolism-related gene expressions were measured.
Results
Cafestol at 60 µM significantly reduced fat accumulation by 20% compared to the control. Cafestol increased locomotor activity by 38% compared to the control. The effects of cafestol on fat accumulation were dependent on daf-12 (a functional homolog of the human FXR) and further confirmed by the upregulation of a DAF-12-target gene, fard-1 (the homolog of the human fatty acid reductase 1). Cafestol's fat-lowering effects were also dependent on tub-1 (an ortholog of the human TUBBY), which is involved in the neurological regulation of energy expenditure. Cafestol upregulated the expression of ech-1.1, involved in fatty acid β-oxidation; however, no effects of cafestol were observed on lipogenesis, lipolysis or lipid uptake and transport.
Conclusions
In conclusion, cafestol regulates lipid metabolism in C. elegans by increasing fatty acid β-oxidation and energy expenditure dependent on daf-12/FXR.
Funding Sources
Brazilian National Counsel of Technological and Scientific Development (CNPq).
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