Abstract
Cholesterol homeostasis in the body is mainly controlled by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1), a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes, functions as a sterol transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion. Therefore, NPC1L1 inhibition has been shown to have beneficial effects on components of themetabolic syndrome such as obesity, insulin resistance, and fatty liver. Hence, inflammatory response represents the common soil of obesity-related multi-factorial diseases, the development of more efficient and safer drug lowering cholesterol uptake and decreasing triglyceride seems to be ideal future drug for NAFLD and inflammation-based carcinogenesis. We have developed egg yolk IgY specifically targeted for NPC1L1 designed to block enteric cholesterol transport and documented the more efficient blocking efficacy of IgY targeted for NPC1L1 than ezetimibe, specifically binding affinity to NPC1L1 and potency of inhibiting cholesterol transport. In high fat diet-fed SD rats, IgY targeted for NPC1L1 showed significantly decreased triglyceride levels as well as LDL than control group and higher effects than ezetimibe treated group (60.21±8.69 vs 69.8±7.66, p=0.012). On pathology of liver, IgY treated group showed significantly improved pathology of NAFLD than ezetimibe or control group (grade of steatosis p<0.001). Significantly improved scores of hepatic inflammation reflected with significant lowering SGOT and SGPT (p<0.05). Since IgY is easy to extract and purify, we anticipate the administration of IgY under the warranted safety can be a potential application for NAFLD and associated hepatocarcinogenesis.
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