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
MetadataShow full item record
AuthorGámez 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 dietMetabolic syndromeBiliary acidsTissue non-specific alkaline phosphatase
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]
SponsorshipMinistry of Economy and Competitivity of Spain; European Commission BFU2014-57736-P AGL2014-58883-R SAF2017-88457-R AGL2017-85270-R; Junta de Andalucia CTS235 CTS164; Ministry of Education; Instituto de Salud Carlos III European Commission
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.