Work

Quercetin’s regulation of glucose and lipid metabolism in gestational diabetes mellitus: role of the PCSK9/LDLR axis

Year: 2025

Type: article

Abstract: This study explored the ability of quercetin to improve glucose and lipid metabolism disorders induced by a high-fat diet (HFD) in a mouse model of gestational diabetes mellitus (GDM) on the basis of the PCSK9/LDLR axis and its potential molecular mechanisms. For the animal experiments, pregnant C57BL/6J mice were randomly divided into three groups: the control group (CD group), which was fed a standard diet; the model group (HFD group), which was fed a HFD; and the quercetin (CAS: 117–39–5) intervention group (HQ group), which was fed a HFD and given 75 mg·kg− 1·day− 1 quercetin by gavage. Moreover, we created an in vitro GDM hepatocyte model in which BNL CL.2 cells were cultured in high glucose and treated with 16 µM quercetin. The results showed that quercetin significantly improved glucose tolerance in GDM mice, reduced serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. It also alleviated hepatic steatosis and pancreatic islet cell hypertrophy. Additionally, it improved the abnormal weights of the placenta and fetus. In in vitro experiments, quercetin regulated the PCSK9/LDLR axis and activated the PI3K/AKT/GSK3β signaling pathway, increasing glucose uptake in liver cells. Molecular docking experiments confirmed that quercetin could directly occupy the PCSK9 catalytic pocket, with binding energies of -9.056 kcal mol− 1 for PCSK9 (human), -9. 193 kcal mol− 1 for PCSK9(mouse) and − 9.1 kcal mol− 1 for EGF-A interface of LDLR, which would sterically hinder LDLR interaction. This study revealed that quercetin improves glucose and lipid metabolism disorders in a GDM model by regulating the PCSK9/LDLR axis and the PI3K/AKT/GSK3β pathway. These findings support the potential use of quercetin as a treatment strategy for GDM.

Source: Nutrition & Metabolism

DOI: 10.1186/s12986-025-01048-2

Authors: Letong Hong, Shuting Xia, Niankun Chen, Zilian Wang, Zhuyu Li

Institution: The First Affiliated Hospital, Sun Yat-sen University

Language: English

Topic: Natural Antidiabetic Agents Studies

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,590