Long-term intake of a high protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

Handle URI:
http://hdl.handle.net/10754/623292
Title:
Long-term intake of a high protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats
Authors:
Diaz Rua, Ruben; Keijer, Jaap; Palou, Andreu; van Schothorst, Evert M.; Oliver, Paula
Abstract:
Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid–base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid–base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences.
KAUST Department:
Red Sea Research Center (RSRC)
Citation:
Díaz-Rúa R, Keijer J, Palou A, van Schothorst EM, Oliver P (2017) Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats. The Journal of Nutritional Biochemistry 46: 39–48. Available: http://dx.doi.org/10.1016/j.jnutbio.2017.04.008.
Publisher:
Elsevier BV
Journal:
The Journal of Nutritional Biochemistry
Issue Date:
19-Apr-2017
DOI:
10.1016/j.jnutbio.2017.04.008
Type:
Article
ISSN:
0955-2863
Sponsors:
We thank Enzo Ceresi and Paula Núñez for technical assistance in the immunohistochemistry and Western blot analysis, respectively.
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0955286316303333
Appears in Collections:
Articles; Red Sea Research Center (RSRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorDiaz Rua, Rubenen
dc.contributor.authorKeijer, Jaapen
dc.contributor.authorPalou, Andreuen
dc.contributor.authorvan Schothorst, Evert M.en
dc.contributor.authorOliver, Paulaen
dc.date.accessioned2017-04-30T10:17:00Z-
dc.date.available2017-04-30T10:17:00Z-
dc.date.issued2017-04-19en
dc.identifier.citationDíaz-Rúa R, Keijer J, Palou A, van Schothorst EM, Oliver P (2017) Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats. The Journal of Nutritional Biochemistry 46: 39–48. Available: http://dx.doi.org/10.1016/j.jnutbio.2017.04.008.en
dc.identifier.issn0955-2863en
dc.identifier.doi10.1016/j.jnutbio.2017.04.008en
dc.identifier.urihttp://hdl.handle.net/10754/623292-
dc.description.abstractIntake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid–base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid–base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences.en
dc.description.sponsorshipWe thank Enzo Ceresi and Paula Núñez for technical assistance in the immunohistochemistry and Western blot analysis, respectively.en
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0955286316303333en
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in The Journal of Nutritional Biochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The Journal of Nutritional Biochemistry, [, , (2017-04-19)] DOI: 10.1016/j.jnutbio.2017.04.008 . © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectLiver steatosisen
dc.subjectLiver diseaseen
dc.subjectHyperproteic dieten
dc.subjectAcid loaden
dc.subjectMicroarray analysisen
dc.titleLong-term intake of a high protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in ratsen
dc.typeArticleen
dc.contributor.departmentRed Sea Research Center (RSRC)en
dc.identifier.journalThe Journal of Nutritional Biochemistryen
dc.eprint.versionPost-printen
dc.contributor.institutionLaboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spainen
dc.contributor.institutionHuman and Animal Physiology, Wageningen University, Wageningen, the Netherlandsen
kaust.authorDiaz Rua, Rubenen
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