Effect of Ezetimibe on Glucose Metabolism and Inflammatory Markers in Adipose Tissue

Abstract

Despite numerous studies, the effects of ezetimibe on glucose metabolism are poorly understood. Here, we aimed to investigate the effects of ezetimibe on glucose metabolism and the expression of inflammatory markers. Thirteen rats were randomly assigned to an ezetimibe (n = 6) or control group (n = 7). The control group received a high fat diet (HFD; 60 Kcal%), whereas the ezetimibe group received an HFD (60 Kcal%) containing 160 mg/kg of ezetimibe. After 14 weeks, adipose and liver tissues, along with plasma, were collected and comparatively analyzed. The effects of combination therapy with ezetimibe and statins on glucose metabolism were investigated over a 1-year period using data from patients with hyperlipidemia. Several indices of glucose metabolism partially improved in the ezetimibe group. The sizes of adipocytes and the accumulation of pro-inflammatory cytokines were reduced in the ezetimibe group. Ezetimibe treatment induced anti-inflammatory cytokines and fatty acid oxidation in adipocytes and reduced serum levels of free fatty acids. Clinical data analysis revealed that statin monotherapy significantly increased insulin resistance. However, combination therapy with ezetimibe and statins did not increase insulin resistance. In conclusion, ezetimibe was found to reduce the sizes of adipocytes in visceral fat and serum levels of free fatty acids, to induce fatty acid oxidation, to improve adipocytic inflammation, and to partially improve glycemic index values.