Sargahydroquinoic acid, a major compound in Sargassum serratifolium (C. Agardh) C. Agardh, widely activates lipid catabolic pathways, contributing to the formation of beige-like adipocytes

Abstract

Sargassum serratifolium (C. Agardh) C. Agardh, a marine brown alga, has been consumed as food and traditional medicine in Asia. Previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (C. Agardh) C. Agardh (MES) stimulated adipose tissue browning and inhibited diet-induced obesity and metabolic syndrome. Sargahydroquinoic acid (SHQA) is a major component in MES. It is investigated whether SHQA is a contributor for the anti-obesity effect of MES and whether SHQA directly acts on adipocytes using 3T3-L1 differentiated under the classical and beige adipocyte-inducing conditions. Interestingly, SHQA notably reduced lipid accumulation despite the upregulation of adipogenic transcription factor PPARγ in adipocytes differentiated under both conditions. Western blotting and protein-ligand docking simulation further revealed that SHQA also activates PPARα and AMPKα, lipid-catabolic proteins. Thus, it is further focused on the signaling pathways mediated by these proteins. SHQA markedly elevated lipolysis and mitochondria number, but paradoxically reduced ATP production. When uncoupled metabolic signaling was examined, SHQA significantly increased UCP1-positive adipocytes as well as beige adipocyte markers. In conclusion, SHQA may activate PPARγ, PPARα, and AMPKα, contributing to the stimulation of lipid catabolic pathways and adipocyte browning. Therefore, SHQA may be used as a novel pharmaceutical agent to combat obesity and associated metabolic syndrome.

Keywords

• Adipocyte browning
• Sargahydroquinoic acid
• 3T3-L1
• Lipolysis
• Mitochondria