Caveolin-1 deficiency alleviates palmitate-induced intracellular lipid accumulation and inflammation in pancreatic β cells

Lipotoxicity-induced pancreatic beta cell damage is a strong predictor of type 2 diabetes mellitus (T2DM). Our previous work showed that Caveolin-1 (Cav-1) depletion decreased beta-cell apoptosis and improved beta-cell viability. Further microarray analysis indicated significant changes in the expression of genes related to fatty acid metabolism and inflammation. The objective of this study was to explore the role of Cav-1 in intracellular lipid accumulation and inflammation in beta cells under lipotoxic conditions. Here, we established a beta-cell-specific Cav-1 knockout (beta-Cav-1 KO) mouse model and a CAV-1 depleted beta cell line (NIT-1). We found that Cav-1 silencing significantly reduced palmitate (PA)-induced intracellular triglyceride (TG) accumulation and decreased proinflammatory factor expression in both the mouse and cell models. Further mechanistic investigation revealed that amelioration of lipid metabolism was achieved through the downregulation of lipogenic markers (SREBP-1c, FAS and ACC) and upregulation of a fatty acid oxidation marker (CPT-1). Meanwhile, decrease of inflammatory cytokines (IL-6, TNF-alpha, and IL-1 beta) secretion was found with the involvement of the IKK beta/NF-kappa B signaling pathways. Our findings suggest that Cav-1 is of considerable importance in regulating lipotoxicity-induced beta-cell intracellular lipid accumulation and inflammation.

Automated summary

Cav-1 plays an important role in regulating lipotoxicity-induced intracellular lipid accumulation and inflammation in pancreatic beta cells, reducing intracellular triglyceride accumulation induced by fatty acids and decreasing the expression of inflammatory factors.