Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition

Handle URI:
http://hdl.handle.net/10754/622420
Title:
Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition
Authors:
Diaz Rua, Ruben; Van Schothorst, E. M.; Keijer, J.; Palou, A.; Oliver, P.
Abstract:
Background/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.
KAUST Department:
Red Sea Research Center (RSRC)
Citation:
Díaz-Rúa R, van Schothorst EM, Keijer J, Palou A, Oliver P (2016) Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition. International Journal of Obesity 40: 1250–1259. Available: http://dx.doi.org/10.1038/ijo.2016.47.
Publisher:
Springer Nature
Journal:
International Journal of Obesity
Issue Date:
22-Mar-2016
DOI:
10.1038/ijo.2016.47
Type:
Article
ISSN:
0307-0565; 1476-5497
Sponsors:
We thank Enzo Ceresi for technical assistance in the morphological and immunohistochemical analysis. CIBER de Fisiopatologia de la Obesidad y Nutricion is an initiative of the ISCIII. This work was supported by the Spanish Government (Ministerio de Educacion y Ciencia, EPIMILK (AGL2012-33692)) and by the EU FP7 project (BIOCLAIMS (FP7-244995)). Laboratory of Molecular Biology, Nutrition and Biotechnology and Human and Animal Physiology are members of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004-506360 NUGO). RD-R was recipient of a fellowship from the Spanish Government.
Appears in Collections:
Articles; Red Sea Research Center (RSRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorDiaz Rua, Rubenen
dc.contributor.authorVan Schothorst, E. M.en
dc.contributor.authorKeijer, J.en
dc.contributor.authorPalou, A.en
dc.contributor.authorOliver, P.en
dc.date.accessioned2017-01-02T09:28:30Z-
dc.date.available2017-01-02T09:28:30Z-
dc.date.issued2016-03-22en
dc.identifier.citationDíaz-Rúa R, van Schothorst EM, Keijer J, Palou A, Oliver P (2016) Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition. International Journal of Obesity 40: 1250–1259. Available: http://dx.doi.org/10.1038/ijo.2016.47.en
dc.identifier.issn0307-0565en
dc.identifier.issn1476-5497en
dc.identifier.doi10.1038/ijo.2016.47en
dc.identifier.urihttp://hdl.handle.net/10754/622420-
dc.description.abstractBackground/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.en
dc.description.sponsorshipWe thank Enzo Ceresi for technical assistance in the morphological and immunohistochemical analysis. CIBER de Fisiopatologia de la Obesidad y Nutricion is an initiative of the ISCIII. This work was supported by the Spanish Government (Ministerio de Educacion y Ciencia, EPIMILK (AGL2012-33692)) and by the EU FP7 project (BIOCLAIMS (FP7-244995)). Laboratory of Molecular Biology, Nutrition and Biotechnology and Human and Animal Physiology are members of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004-506360 NUGO). RD-R was recipient of a fellowship from the Spanish Government.en
dc.publisherSpringer Natureen
dc.titleIsocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat depositionen
dc.typeArticleen
dc.contributor.departmentRed Sea Research Center (RSRC)en
dc.identifier.journalInternational Journal of Obesityen
dc.contributor.institutionLaboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, CIBER de Fisiopatolog'a de la Obesidad y Nutrición (CIBERobn), Cra. Valldemossa Km 7.5, Palma de Mallorca, E-07122, Spainen
dc.contributor.institutionHuman and Animal Physiology, Wageningen University, Wageningen, Netherlandsen
kaust.authorDiaz Rua, Rubenen
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