Berberine reduces hepatic ceramide levels to improve insulin resistance in HFD-fed mice by inhibiting HIF-2α - 27/05/22
Abstract |
Several studies have documented the effects of hypoxia and ceramides on lipid and glucose metabolism, resulting in insulin resistance. However, the roles of ceramide in hepatic hypoxia and hepatic insulin resistance remain to be clarified. This study aimed to explore the relationship between hypoxia, ceramide synthesis, and hepatic insulin resistance in high-fat diet (HFD)-fed mice. Given the interaction of hypoxia-inducible factors 2α(HIF-2α) and berberine determined using molecular docking, this study also assessed the pharmacological effects of berberine on the HIF-2α-ceramide-insulin resistance pathway. In the preliminary phase of the study, gradually aggravated hepatic hypoxia and varying levels of ceramides were observed with the development of type 2 diabetes mellitus (T2DM) due to increasing HIF-2α accumulation. Lipidomic analyses of animal and cell models revealed that berberine reduced hypoxia-induced ceramide production and attenuated ceramide-induced insulin resistance. This research provides timely and necessary evidence for the role of ceramide in hypoxia and insulin resistance in the liver. It also contributes to a better understanding of the pharmacological effects of berberine on ameliorating hypoxia and insulin resistance in T2DM therapy.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Elevated HIF-2 expression, insulin resistance, and disorder lipid metabolism in liver of HFD-induced mice. |
• | BBR decreases HIF-2 expression and the ceramides related to insulin resistance. |
• | BBR promotes glycogen synthesis via the PP2A-AKT-GSK3 signaling pathway. |
• | BBR alleviates glucose and lipid metabolism by inhibiting HIF-2 . |
Keywords : Ceramide, Hypoxia-inducible factor-2α, Hepatic insulin resistance, Berberine
Plan
Vol 150
Article 112955- juin 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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