Filbertone, (2E)-5-methyl-2-hepten-4-one, regulates thermogenesis and lipid metabolism in skeletal muscle of a high-fat diet fed mice

Abstract

Filbertone, the principal flavor compound of hazelnuts, is known to have preventive effects against hypothalamic inflammation, obesity and adipocity in vitro and in vivo. However, the effect of filbertone in skeletal muscle remains unknown. In the present study, we determined the effect of filbertone in skeletal muscle of mice fed a high-fat diet (HFD). To identify the underlying molecular and cellular processes of filbertone, we performed whole transcriptome sequencing in skeletal muscle. The muscle transcriptome analysis revealed that the upregulated differentially expressed genes (DEGs) in filbertone-fed mice were substantially associated with several pathways including thermogenesis, fatty acid degradation, oxidative phosphorylation, and branched chain amino acids (BCAAs) degradation. Furthermore, the expression level of thermogenic genes such as uncoupling protein 1 (Ucp1; p < 0.05), cell death-inducing DNA fragmentation factor alpha-like effector A (Cidea; p < 0.05), peroxisome proliferator-activated receptor alpha (Ppara; p < 0.05) and lipid droplet-associated protein genes such as Plin3 (p < 0.05), Plin4 (p < 0.05), and Plin5 (p < 0.05) were significantly upregulated in muscle tissue of HFD with filbertone fed mice compared to HFD only fed mice. Filbertone also elevated the protein level of UCP1 (p < 0.05) and PPARα (p < 0.05). In addition, filbertone reduced the accumulation of intracellular lipids in C2C12 myotubes (p < 0.05). On the basis of these results, we suggest that filbertone has a crucial effect in the regulation of muscle lipid metabolism and energy balance.