Hepatic Mcpip1 regulates adaptation to food restriction in mice

Olga Mucha; Bozena Skupien-Rabian; Alicja Slota; Katarzyna Trzos; Natalia Pydyn; Bartosz Podlewski; Jolanta Jura; Jerzy Kotlinowski

doi:10.18388/abp.2020_6819

Olga Mucha Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland
Bozena Skupien-Rabian Jagiellonian University, Malopolska Centre of Biotechnology, Proteomics and Mass Spectrometry Core Facility, Kraków, Poland
Alicja Slota Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland
Katarzyna Trzos Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland
Natalia Pydyn Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland
Bartosz Podlewski Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland
Jolanta Jura Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland
Jerzy Kotlinowski Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Kraków, Poland

DOI: https://doi.org/10.18388/abp.2020_6819

Abstract

Monocyte-chemoattractant protein-induced protein 1 (MCPIP1, or Regnase-1) is an endoribonuclease that degrades translationally active mRNA molecules. MCPIP1 is mostly known for its anti-inflammatory actions, but it is also an important regulator of adipogenesis and lipid metabolism. Its overexpression impairs adipogenesis by reducing mRNA levels of C/EBPβ and PPARγ, key transcription factors regulating this process. Although adipocytes overexpressing MCPIP1 are characterised by impaired glucose uptake, the function of MCPIP1 in hepatocyte metabolism remains unknown. In this study, conditional deletion of Zc3h12a in murine liver epithelial cells was used to characterise the role of Mcpip1 in adaptation to 24-hour food restriction. We found that Mcpip1 deficiency in liver epithelial cells (Mcpip1^fl/flAlb^Cre mice) resulted in higher blood glucose levels in response to fasting in comparison to Mcpip1^fl/fl counterparts. Hepatic proteome analysis showed 26 down-regulated and 117 up-regulated proteins in Mcpip1^fl/flAlb^Cre animals that were involved in cellular adhesion, extracellular matrix and metabolic processes. In conclusion, our studies provide new insight into the hepatic function of Mcpip1 and its involvement in metabolic control.