Cafestol increases fat oxidation and energy expenditure in Caenorhabditis elegans via DAF-12-dependent pathway

• Published in: Food chemistry Vol. 307; p. 125537
• Main Authors: Farias-Pereira, Renalison, Kim, Edward, Park, Yeonhwa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2020
• Subjects: Animals; C. elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - enzymology; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Cafestol; Coffee; Diterpene; Diterpenes - pharmacology; Energy Metabolism; Enoyl-CoA Hydratase - metabolism; Humans; Lipid Metabolism; Obesity; Receptors, Cytoplasmic and Nuclear - metabolism; Signal Transduction; Diterpene; Obesity; C. elegans; Coffee; Cafestol
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2019.125537

•Cafestol regulates fatty acid metabolism in Caenorhabditis elegans.•daf-12, the homolog of farnesoid X receptor, is a target for cafestol.•Cafestol’s fat-lowering effects require tub-1, the ortholog of mammalian TUBBY.•Cafestol increases fat oxidation/energy expenditure dependent on DAF-12 and TUB-1. Cafestol, a coffee diterpene, is a known agonist of farnesoid X receptors (FXR), which are involved in cholesterol homeostasis. FXR plays critical roles in other lipid metabolic pathways, including fat oxidation; however, little is known about cafestol’s effects on fatty acid metabolism. Thus, the goal was to investigate cafestol’s effects on fatty acid metabolism using Caenorhabditis elegans. Cafestol at 60 µM reduced fat accumulation and increased locomotor activity (an indicator of energy expenditure) by 20% and 38%, respectively, compared to the control. Cafestol’s effects were dependent on daf-12 (a functional homolog of the human FXR) with upregulation of ech-1.1 (a homolog of enoyl-CoA hydratase involved in fatty acid β-oxidation) and tub-1 (an ortholog of the human TUBBY involved in the neurological regulation of energy expenditure) without any effects on lipogenesis, lipolysis or lipid uptake and transport. Therefore, cafestol increased fat oxidation and energy expenditure via DAF-12-dependent pathway in C. elegans.