Ezetimibe ameliorates atherogenic lipids profiles, insulin resistance and hepatocyte growth factor in obese patients with hypercholesterolemia

Abstract

BackgroundEzetimibe ameliorates serum low-density lipoprotein cholesterol (LDL-c) and it has been approved for the treatment of hypercholesterolemia. However, the effects of ezetimibe on specific biomarkers have not been fully clarified in obese Japanese patients.MethodsA total of 101 patients (47 males and 54 females) were registered in this study during 2011 and 2012. All patients were over 20 years old, were obese [body mass index (BMI) ≥ 25kg/m2] and had hypercholesterolemia (LDL-c ≥ 120mg/dl). After excluding 10 subjects (7 who dropped out and 3 with missing data), 91 patients (39 males and 52 females) were analyzed. They were treated with 10 mg ezetimibe once a day for 24 weeks and were evaluated at 12 and 24 weeks.ResultsFollowing 12 weeks of ezetimibe therapy, BMI (p < 0.001), waist circumference (p < 0.001), total cholesterol (p < 0.001), LDL-c (p < 0.001), non high-density lipoprotein cholesterol [HDL-c] (p < 0.001), triglycerides (p < 0.05) and remnant-like particle cholesterol (RLP-c; p < 0.001) were significantly decreased. Following 24 weeks of ezetimibe therapy, BMI (p < 0.05), waist circumference (p < 0.001), total cholesterol (p < 0.001), LDL-c (p < 0.001), non HDL-c (p < 0.001), triglycerides (p < 0.05), RLP-c (p < 0.001), insulin (p < 0.05) and hepatocyte growth factor (HGF; p < 0.05) were significantly decreased. In contrast, HDL-c (p < 0.001) was significantly increased.ConclusionsEzetimibe ameliorated not only atherogenic lipid profiles but also anthropometric factors, insulin resistance and biomarkers such as HGF. Ezetimibe may have pleiotropic effects on obese patients with hypercholesterolemia.

Comparison of the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy and Rosuvastatin Monotherapy on Lipoprotein in Patients With Type 2 Diabetes: Multicenter Randomized Controlled Study

“…Several studies have reported an effect of statins on glucose metabolism [23,[31][32][33][34] and on the risk of new-onset diabetes [35,36], but the results remain controversial. Results from earlier studies also suggest that ezetimibe could improve insulin resistance [37][38][39]. Two studies reported that the addition of ezetimibe to a statin as combination therapy improved insulin resistance and did not increase the risk of diabetes [40,41].…”

Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model

“…It has also been shown in humans that adopting a Nordic diet (which includes high fish consumption), leads to reduction in some plasma CER[ NS ] ceramides, although the originating tissue of these species is unknown [66]. This variation between tissue responses is evident within the same animal, as mice on fish oil- or krill oil-supplemented diets had decreased CER[ NS ] and CER[ NDS ] ceramides in the liver, and increased CER[ NS ] and CER[ NDS ] ceramides in the brain [67]. Increased ceramide production has also been seen in breast cancer cells following EPA or DHA supplementation in vitro , or fish oil supplementation in vivo , through increased neutral sphingomyelinase activity [68].…”

Galectin-3 and IL-33/ST2 axis roles and interplay in diet-induced steatohepatitis

“…Increased lipolysis in adipose tissue and increased plasma free fatty acids together with metaflammation are believed to promote lipid accumulation in hepatocytes leading to liver steatosis[27,28]. The pathogenesis of fibrotic NASH is described in a “two-hit hypothesis”, wherein insulin resistance acts as “first hit” that leads to liver steatosis which renders hepatocytes more susceptible to a “second hit” which could involve inflammatory and oxidative stress mediators, lipotoxic fatty acids, cholesterol and ceramides[29].…”