Progesterone and lipoline receptor 3 (PAQR3) regulates the mechanism of liver lipid metabolism.

Recently, the Chinese Academy of Sciences Shanghai Institute of Life Sciences (population health field) Chen Wei research group found that progesterone and lipoline receptor 3 (PAQR3) by promoting PPAR alpha ubiquitin and protease pathway dependence degradation, and thus regulate the mechanism of liver lipid metabolism.
peroxidase proliferation activates receptor alpha (PPAR alpha) to maintain a steady state of energy metabolism in the body.
when the body is in a state of nutritional deficiency, PPAR alpha in the package will be transferred to the nucleus of the cell, the nucleus of PPAR alpha will promote downstream participation in the expression of fatty acid oxidation-related genes, thereby promoting fatty acid oxidation, to ensure the normal energy needs of the body and maintain the liver lipid metabolism steady state.
fatty acid oxidation is one of the main pathways of liver lipid metabolism, if the accumulation of lipids in the liver can not be metabolized in time will cause lipid accumulation in the liver, serious cases will cause liver fat degeneration and then lead to non-alcoholic fatty liver.
studies have shown that a high-fat diet induces severe fatty liver disease in mice with PPAR alpha liver-specific knockout, but the mechanism by which PPAR alpha's post-translation modification regulates liver lipid metabolism is not clear.
Under the guidance of researcher Chen Wei, Ph.D. student Zhao Zilong and others found that PAQR3 in the liver of mice can affect the accumulation of triglycerides in the liver caused by prolonged fasting using adenovirus interference techniques.
mice that were struck by creating liver-specific PAQR3 knockoutfounds found that PAQR3 knockout mice were able to reduce fatty liver formation caused by prolonged fasting.
through a series of biochemical and cellular experiments, the researchers found that PAQR3 can affect the protein levels of PPAR alpha without changing its mRNA levels, PAQR3 can promote the ubiquitization of PPAR alpha protein and thus affect the half-life of PPAR alpha, and further studies have found that the E3 ubiquitin connective enzyme HUWE1 involved in PPAR alpha degradation.
this study provides a new theoretical basis for in-depth understanding of the molecular mechanism in the steady balance of liver lipids, and also shows that in-depth discussion of the PAQR3-HUWE1-PPAR alpha signaling pathway can provide new therapeutic targets and ideas for the treatment of non-alcoholic fatty liver and other metabolic diseases.
research published in hepatology.
the research was supported by the National Natural Science Foundation of China, the National Key Basic Research and Development Program, the Chinese Academy of Sciences, and Liao Lujian, a professor at East China Normal University.
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