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Ferulic acid ameliorates high-fat diet-induced hyperlipidemia in mice via suppressing the PGC-1β/miR-378a-3p axis
Kaili Cui1, Meihong Chen2, Lichao Zhang3
1Central Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China; Institute of Biotechnology, the Biomedical and Health Laboratory in Shanxi Province, Shanxi University, Taiyuan, Shanxi, China.
Abstract:
Hyperlipidemia (HLP) has emerged as a prevalent chronic metabolic disorder and seriously threatens human health. Given the limitations of current pharmacotherapies, the exploration of safe and effective natural bioactive compounds for HLP management has become an urgent research priority. Ferulic acid (FA), a common dietary phenolic compound, exhibits significant lipid-lowering effects. This study investigates the underlying molecular mechanisms of FA in HLP. It was found that FA supplementation significantly alleviated HLP phenotypes in a dose-dependent manner, without inducing obvious toxic side effects on major organs. In vitro, FA effectively suppressed free fatty acid-induced lipid accumulation in hepatocytes. Mechanistically, FA significantly downregulated the expression of miR-378a-3p, a well-characterized HLP-associated microRNA. The reduced miR-378a-3p further inhibited very low-density lipoprotein secretion and activated fatty acid oxidation, contributing to the lipid-lowering effects of FA. Importantly, we identified that FA inhibited miR-378a-3p expression by suppressing the peroxisome proliferator-activated receptor (PPAR) gamma-coactivator-1beta/liver X receptor α axis. Collectively, this study uncovered a potential regulatory pathway through which FA ameliorates HLP, providing experimental evidence for FA as a potential natural dietary supplement for the prevention and management of HLP.
Insights
Ferulic acid (FA) effectively lowers lipids in hyperlipidemia (HLP) by reducing miR-378a-3p expression. This natural compound offers a promising, safe dietary supplement for managing HLP.
Area of Science:
- Biochemistry
- Metabolic Disorders
- Nutraceuticals
Background:
- Hyperlipidemia (HLP) is a widespread metabolic disorder with significant health implications.
- Current pharmacotherapies for HLP have limitations, driving the search for natural alternatives.
- Ferulic acid (FA), a dietary phenolic compound, shows potential for lipid-lowering effects.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the lipid-lowering effects of Ferulic acid (FA) in hyperlipidemia (HLP).
- To evaluate the safety and efficacy of FA as a potential natural supplement for HLP management.
Main Methods:
- In vivo and in vitro studies using animal models and cell cultures (hepatocytes) to assess FA's effects on HLP phenotypes.
- Analysis of gene and miRNA expression, including miR-378a-3p, PGC-1β, and LXRα.
- Assessment of lipid accumulation, Very Low-Density Lipoprotein (VLDL) secretion, and fatty acid oxidation.
Main Results:
- FA supplementation dose-dependently alleviated HLP phenotypes without significant organ toxicity.
- FA suppressed free fatty acid (FFA)-induced lipid accumulation in hepatocytes.
- FA downregulated miR-378a-3p expression, inhibited VLDL secretion, and activated fatty acid oxidation.
- FA's mechanism involves suppressing the PGC-1β/LXRα axis, leading to reduced miR-378a-3p expression.
Conclusions:
- FA ameliorates HLP by modulating the PGC-1β/LXRα axis and subsequently downregulating miR-378a-3p.
- These findings provide evidence for FA as a potential natural dietary supplement for HLP prevention and management.
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