Deficiency in Tissue Non-Specific Alkaline Phosphatase Leads to Steatohepatitis in Mice Fed a High Fat Diet Similar to That Produced by a Methionine and Choline Deficient Diet Gámez Belmonte, María de los Reyes Tena Garitaonaindia, Mireia Hernández Chirlaque, Cristina Córdova, Samir Ceacero-Heras, Diego Sánchez De Medina López-Huertas, Fermín Martínez Augustín, María Olga Methionine and choline diet Metabolic syndrome Biliary acids Tissue non-specific alkaline phosphatase Funding: This research was funded by the Ministry of Economy and Competitivity of Spain, partly with Fondo Europeo de Desarrollo Regional FEDER funds [BFU2014-57736-P, AGL2014-58883-R, SAF2017-88457-R, AGL2017-85270-R] and by Junta de Andalucía [CTS235, CTS164]. MTG, RGB and CHC were supported by fellowships from the Ministry of Education. CIBERehd is funded by Instituto de Salud Carlos III. Institutional Review Board Statement: The study was conducted according to the guidelines of the Guide for the Care and Use of Laboratory Animals, and approved by the Animal Welfare Committee of the University of Granada (registry number: CEEA 01/03/2017–029). Informed Consent Statement: Not applicable for studies not involving humans. Acknowledgments: We gratefully acknowledge the assistance of Mercedes González and the rest of the group. The liver expresses tissue-nonspecific alkaline phosphatase (TNAP), which may participate in the defense against bacterial components, in cell regulation as part of the purinome or in bile secretion, among other roles. We aimed to study the role of TNAP in the development of hepatosteatosis. TNAP+/− haplodeficient and wild type (WT) mice were fed a control diet (containing 10% fat w/w) or the same diet deficient in methionine and choline (MCD diet). The MCD diet induced substantial weight loss together with hepatic steatosis and increased alanine aminotransferase (ALT) plasma levels, but no differences in IL-6, TNF, insulin or resistin. There were no substantial differences between TNAP+/− and WT mice fed the MCD diet. In turn, TNAP+/− mice receiving the control diet presented hepatic steatosis with alterations in metabolic parameters very similar to those induced by the MCD diet. Nevertheless, no weight loss, increased ALT plasma levels or hypoglycemia were observed. These mice also presented increased levels of liver TNF and systemic resistin and glucagon compared to WT mice. The phenotype of TNAP+/− mice fed a standard diet was normal. In conclusion, TNAP haplodeficiency induces steatosis comparable to that produced by a MCD diet when fed a control diet. 2021-02-25T08:55:45Z 2021-02-25T08:55:45Z 2020-12-23 journal article Gámez-Belmonte, R.; Tena-Garitaonaindia, M.; Hernández- Chirlaque, C.; Córdova, S.; Ceacero- Heras, D.; de Medina, F.S.; Martínez- Augustin, O. Deficiency in Tissue Non- Specific Alkaline Phosphatase Leads to Steatohepatitis in Mice Fed a High Fat Diet Similar to That Produced by a Methionine and Choline Deficient Diet. Int. J. Mol. Sci. 2021, 22, 51. [https://dx.doi.org/10.3390/ijms22010051] http://hdl.handle.net/10481/66715 10.3390/ijms22010051 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI