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Lipid Accumulation in HepG2 Cells Is Attenuated by Strawberry Extract through AMPK Activation
Tamara Y Forbes-Hernández1,2, Francesca Giampieri3, Massimiliano Gasparrini4
1Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, 60131 Ancona, Italy. tamara.forbe@gmail.com.
Abstract:
Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2). For such purpose, the lipid profile and the expression of proteins metabolically related to AMPK were determined on cells lysates. The results demonstrated that strawberry methanolic extract decreased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides levels (up to 0.50-, 0.30-, and 0.40-fold, respectively) while it stimulated the p-AMPK/AMPK expression (up to 3.06-fold), compared to the control. AMPK stimulation led to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively. Strawberry treatment also entailed a 4.34-, 2.37-, and 2.47-fold overexpression of LDL receptor, sirtuin 1 (Sirt1), and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), respectively, compared to control. The observed results were counteracted by treatment with compound C, an AMPK pharmacological inhibitor, confirming that multiple effects of strawberries on lipid metabolism are mediated by the activation of this protein.
Insights
Methanolic strawberry extract improves lipid metabolism by activating AMP-activated protein kinase (AMPK). This reduces cholesterol and triglycerides, and influences key regulatory proteins, offering potential for chronic disease management.
Area of Science:
- Biochemistry
- Cell Biology
- Nutritional Science
Background:
- Lipid metabolism dysregulation is central to chronic diseases like obesity and cardiovascular disease.
- AMP-activated protein kinase (AMPK) is a key regulator of cellular energy and lipid metabolism.
- Dietary compounds are increasingly investigated for their role in modulating metabolic pathways.
Purpose of the Study:
- To investigate the in vitro effects of a methanolic strawberry extract on AMPK signaling.
- To determine the impact of strawberry extract on lipid metabolism in human liver cells (HepG2).
- To elucidate the molecular mechanisms underlying strawberry's effects on lipid regulation.
Main Methods:
- Treatment of HepG2 cells with methanolic strawberry extract.
- Analysis of cellular lipid profiles, including total cholesterol, LDL-cholesterol, and triglycerides.
- Western blot analysis to assess the expression and phosphorylation of AMPK and related proteins (ACC, HMGCR).
- Measurement of LDL receptor, Sirt1, and PGC-1α expression.
- Validation using an AMPK inhibitor (Compound C).
Main Results:
- Strawberry extract significantly reduced total cholesterol, LDL-cholesterol, and triglyceride levels.
- Extract treatment increased the phosphorylation and activation of AMPK (p-AMPK/AMPK ratio up to 3.06-fold).
- Activated AMPK led to inactivation of acetyl-CoA carboxylase (ACC) and inhibition of HMGCR.
- Strawberry extract upregulated LDL receptor, Sirt1, and PGC-1α expression.
- Inhibition of AMPK with Compound C reversed the observed effects.
Conclusions:
- Methanolic strawberry extract effectively modulates lipid metabolism in HepG2 cells.
- The beneficial effects are mediated through the activation of AMPK signaling pathway.
- Strawberry extract influences key enzymes and receptors involved in cholesterol and fatty acid synthesis and uptake.
- These findings highlight the potential of strawberries as a dietary intervention for managing lipid disorders and related chronic diseases.
