title: Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Díaz-Rúa
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: van Schothorst
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Keijer
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Palou
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Oliver
mesh_terms: D050154:Adiposity; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D002149:Energy Intake; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D053530:Keratins, Type I / Q000032:analysis / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D053530:Keratins, Type I; D002784:Cholesterol