WITHDRAWN: Mouse Trefoil Factor 3 (Tff3) Ameliorates Fatty Liver Phenotype via Increasing Peroxisome Proliferator-activated Receptor-α (PPARα) Expression

Abstract

// Xiaojie Wu 1, * , Haiyong Jin 2, * , Yueling Zhang 3 , Mingyuan Dong 3 , Xiaoting Wu 3 , Jiadi Zhou 1 , Weishan Zhuge 4 , Jianjing Yang 5 , Qichuan Zhuge 5 , Xiying Luan 1 , Dexiang Ban 6 , Wenjie Zhu 3 , Yongjun Jin 7 and Jiangnan Xue 1 1 Department of Immunology, Binzhou Medical University, Yantai, China 2 Department of Otorhinolaryngology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 3 Department of Operating Theatre, Binzhou People’s Hospital, Binzhou, China 4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 5 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 6 Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, China 7 Department of Endocrinology, Yantai Affiliate Hospital, Binzhou Medical University, Yantai, China * These authors contributed equally to this work Correspondence to: Jiangnan Xue, email: xuejinagnan@263.net Yongjun Jin, email: endojin@126.com Keywords: nonalcoholic fatty liver disease; mouse trefoil factor 3; peroxisome proliferator-activated receptor-α; fatty acid oxidation; lipogenesis Received: March 03, 2017 Accepted: December 13, 2017 Published: January 02, 2018 ABSTRACT Hepatic trefoil factor 3 (Tff3) was identified as a potential protein for the treatment of diabetes, yet the mechanisms involved in this effect remain unclear. Moreover, the effect of Tff3 on non-alcoholic fatty liver disease (NAFLD) has never been examined. Here, we show that the expression of hepatic Tff3 was significantly decreased in NAFLD mouse models, indicating that Tff3 was a potential marker gene for NAFLD. Restoring the expression of Tff3 in the liver of NAFLD mice including db/db (diabetic), ob/ob (obese) and DIO (diet-induced obese) mice with adenovirus-mediated Tff3 (Ad-Tff3) attenuates the fatty liver phenotype. In contrast, adenovirus-mediated knockdown of Tff3 (Ad-shTff3) in normal C57BL/6J mice results in an obvious fatty liver phenotype. Furthermore, our molecular experiments indicated that hepatic Tff3 could alleviate hepatic steatosis by directly up-regulating the expression of peroxisome proliferator-activated receptor-α (PPARα), thereby enhancing fatty acid oxidation processes in the liver. Notably, we found that Tff3 attenuates the fatty liver phenotype independent of modulation of lipogenesis and enhances anti-inflammatory effects. Overall, our results suggest that hepatic Tff3 could be effectively used as a potential therapy target for the treatment of NAFLD.