Pine (Pinus koraiensis) Nut Oil Ameliorates Cholesterol Homeostasis and Inflammation via Modulating the miR-34a/122 Pathways in the Liver of Rats Fed a High-Cholesterol Diet.

Abstract

Background: Pine (Pinus koraiensis) nut oil (PNO) has been reported to have various beneficial effects on hepatic triglyceride accumulation and atherosclerosis in animal models. MicroRNAs (miRs) are involved in various diseases by modulating physiological processes. However, the mechanism underlying PNO's effects on the regulation of miRs involved in hepatic cholesterol homeostasis and inflammation remains unclear.

Objectives: This study investigated the effects of PNO on the regulation of the miR-34a/122 pathways involved in cholesterol homeostasis and inflammation in the liver using a high-cholesterol diet (HCD) rat model.

Methods: Six-week-old male Sprague-Dawley rats were randomly divided into three groups (n = 8/group) and provided with (1) a cholesterol-free diet, (2) an HCD containing 1% cholesterol and 0.5% cholic acid, or (3) an HCD containing 5% PNO for 4 weeks. Lipid analysis of serum and liver, histological evaluation, and analysis of gene and protein expression were performed.

Results: PNO supplementation in HCD improved hepatic lipid profiles and elevated serum high-density lipoprotein cholesterol compared to the HCD group. PNO significantly upregulated hepatic gene expression levels of liver X receptor α and ATP-binding cassette transporter A1/G1, which are involved in cholesterol efflux (P < 0.05). Gene expressions of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, monocyte chemoattractant protein-1, and inducible nitric oxide synthase were downregulated by PNO (P < 0.05). PNO also suppressed TNF-α and IL-6 protein levels by 22.3% and 17.3%, respectively (P < 0.05). PNO reduced hepatic nuclear factor-kappa B activity by 16.4% and decreased nitric oxide production in the liver and serum (P < 0.05). Furthermore, hepatic miR-34a and miR-122 expressions decreased by 16.4% and 15.7% by PNO, respectively (P < 0.05).

Conclusions: These results suggest that PNO may affect cholesterol homeostasis and inflammation, which are partially associated with the miR-34a/122 pathways in the liver under an HCD.