β-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes

Area of Science:

• Biochemistry
• Metabolic Disorders
• Pharmacology

Background:

• Nonalcoholic fatty liver disease (NAFLD) is a prevalent global health concern.
• Hepatic lipid accumulation is a key characteristic of NAFLD.
• AMP-activated protein kinase (AMPK) plays a crucial role in regulating hepatic lipid metabolism.

Purpose of the Study:

• To screen for medicinal foods that inhibit hepatic lipid accumulation.
• To investigate the mechanism of action for lipid-lowering compounds.
• To identify natural compounds that activate AMPK for NAFLD treatment.

Main Methods:

• Screening of medicinal foods for hepatocytic lipid accumulation inhibition.
• Analysis of clove (Syzygium aromaticum) extracts.
• Investigating the effects of β-caryophyllene on AMPK signaling pathways in HepG2 hepatocytes.
• Measuring lipid accumulation, protein phosphorylation, and gene expression.

Main Results:

• Clove extract significantly inhibits palmitate-inducible lipid accumulation in hepatocytes.
• β-caryophyllene, a component of clove, is identified as the primary suppressor of lipid accumulation.
• β-caryophyllene stimulates AMPK and acetyl-CoA carboxylase 1 (ACC1) phosphorylation.
• β-caryophyllene prevents SREBP-1c nuclear translocation and FoxO1 cytoplasmic translocation via AMPK signaling.
• Downregulation of fatty acid synthase (FAS) and upregulation of adipose triglyceride lipase were observed.
• AMPK activation by β-caryophyllene is mediated by cannabinoid type 2 receptor-dependent Ca2+ signaling.

Conclusions:

• β-caryophyllene demonstrates potential efficacy in preventing and ameliorating nonalcoholic fatty liver disease.
• The findings suggest therapeutic potential for β-caryophyllene in managing metabolic disorders associated with NAFLD.
• Clove and its active compound, β-caryophyllene, represent a promising natural intervention for NAFLD.