RETRACTED: Role of hepatic neuropeptide Y-Y1 receptors in a methionine-cholinedeficient model of non-alcoholic steatohepatitis
Authors: Hua-Kang Li
Min Jiang
Zhi-Hui Zhang
Ping Zhu
Tao ShangGuan
Pan Yang
Wei-Wei Sun
Lin-Yu Li
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Lipase; Neuropeptide Y-Y1 receptors; Non-alcoholic steatohepatitis; Triglyceride hydrolysis.
Affiliations: Department of Cardiology, Southwest Hospital, Third Military Medical University, China., Department of Cardiology, Southwest Hospital, Third Military Medical University, China. Electronic address: .

Abstract:  Aims: NPY-Y1R plays an important role in dietary regulation. Although germline knockdown of NPY-Y1R in mice alleviates high-fat-diet-induced obesity and increases CPT1α levels in the liver, the role of the Y1 receptor in specific tissues has not been studied. Main methods: MCD diet is the most widely used method to establish a model of lean NASH in a short time. We therefore evaluated the role of liver NPY-Y1R in NASH progression. Key findings: In mice with liver-specific knockout of NPY-Y1R (LivKO) and wild-type control littermates fed MCD diet for 4 weeks, NPY-Y1R deficiency significantly decreased body and liver weight. Moreover, NPY-Y1R deletion protected mice against hepatic steatosis and injury. LivKO decreased TG, TC, and FFA levels in the liver and alanine aminotransferase activity in plasma. To clarify the mechanism, we evaluated the key enzymes involved in triglyceride hydrolase and fatty-acid oxidase. Expression of ATGL, CPT1α, and ACO was significantly increased in LivKO mice, whereas expression of fatty-acid synthase was significantly decreased. mRNA expression analysis revealed a marked reduction of genes involved in de-novo lipogenesis and monosaturated fatty-acid synthesis, including sterol-regulatory element-binding protein 1c and fatty-acid synthase. Moreover, liver injury-related factors were significantly decreased in LivKO mice, such as TNF-α, inducible nitric oxide synthase, and MCP-1. Thus, NPY-Y1R deficiency in the liver alleviates lipid deposition and injury. However, NPY-Y1R did not affect inflammation and fibrosis. Significance: NPY-Y1R deficiency in the liver directly suppresses not only hepatic steatosis, but also liver injury, and thus provides a treatment option for NASH. 

Retracted: Yes

PubPeer comments:
 2021 retraction. https: www.sciencedirect.com science article pii S0024320521001958?via%3Dihub Retraction notice to u201cRole of hepatic neuropeptide Y-Y1 receptors in a methionine- cholinedeficient model of non-alcoholic steatohepatitisu201d [Life Sci. 245 (2020) 117356] Wei-WeiSunTao ShangGuanPingZhuHua-KangLiMinJiangPanYangLin-YuLiZhi-HuiZhang Department of Cardiology, Southwest Hospital, Third Military Medical University, China Available online 7 July 2021. This article has been retracted at the request of the Editor-in-Chief. Concern has been raised by a reader about both the inappropriateness of certain methods used to prepare Figures 1A and 3A; as well as the lack of important information including the exact age of the mice and details of the ELISA used. These issues could undermine the scientific grounds of the article. Apologies are offered to readers of the journal that this was not detected during the submission process. ,