Capsaicin supplementation prevents Western-type diet-induced hypercholesterolemia by reducing endoplasmic reticulum stress in apolipoprotein E-deficient mice

Abstract

Abstract Endoplasmic reticulum (ER) stress presents in atherosclerotic lesions of all stages brought on by hypercholesterolemia. This can incur various pathological responses involved in atherosclerosis. Capsaicin has multiple benefits for metabolic diseases; however, its role in attenuating hypercholesterolemia remains unclear. Therefore, we determined whether dietary capsaicin could alleviate ER stress in apolipoprotein E-deficient (ApoE−/−) mice fed a Western-type diet (WD). Metabolic parameters showed that compared with WD-fed ApoE−/− mice, mice supplemented with dietary capsaicin (0.015%, w/w) displayed significantly reduced body and adipose tissue weight and plasma leptin, total cholesterol, and hepatic triglyceride levels for 12 weeks. Capsaicin supplementation also attenuated the protein abundance involved in ER stress in the liver, as well as glucose-related protein 78 localization in the aorta, indicating that capsaicin inhibits diet-induced hypercholesterolemia in part by regulating the protein abundance involved in ER stress. Capsaicin, therefore, may have potential as a therapeutic agent for individuals with diet-induced hypercholesterolemia.