Publication:
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.

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Date

2020-12-21

Authors

Gamez-Belmonte, Reyes
Tena-Garitaonaindia, Mireia
Hernandez-Chirlaque, Cristina
Cordova, Samir
Ceacero-Heras, Diego
de Medina, Fermin Sanchez
Martinez-Augustin, Olga

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MDPI
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Abstract

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.

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MeSH Terms

Alkaline Phosphatase
Alleles
Animals
Choline
Choline Deficiency
Diet
Diet, High-Fat
Disease Models, Animal
Enzyme Activation
Fatty Liver
Methionine
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases
PPAR alpha
Proto-Oncogene Proteins c-akt
Signal Transduction

DeCS Terms

Activacion Enziatica
Deficiencia de Colina
Fosfatasa Alcalina
PPAR alfa
Mitogenos

CIE Terms

Keywords

Biliary acids, Metabolic syndrome, Methionine and choline diet, Steatohepatitis, Tissue non-specific alkaline phosphatase

Citation

Gámez-Belmonte R, Tena-Garitaonaindia M, Hernández-Chirlaque C, Córdova S, Ceacero-Heras D, de Medina FS. at all. 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. 2020 Dec 23;22(1):51