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

• Published in: International Journal of Obesity 2016-08, Vol.40 (8), p.1250-1259
• Main Authors: Díaz-Rúa, R, van Schothorst, E M, Keijer, J, Palou, A, Oliver, P
• Format: Article
• Language: English
• Subjects: 13/1; 14/63; 38/61; 631/1647/767/1424; 631/443/319/2723; 631/45/287/1182; 692/53; 692/699/1702/393; 692/700/2814; 82/51; 82/80; Adaptation; Adiposity; Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blotting, Western; Body Weight; Carbohydrates; Cholesterol; Cholesterol - blood; Cholesterol - metabolism; Deposition; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Down-Regulation; Energy Intake; Epidemiology; Fat metabolism; Fatty liver; Fatty Liver - etiology; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Food consumption; Fysiologie van Mens en Dier; Gene expression; Genomes; Health aspects; Health Promotion and Disease Prevention; High fat diet; Human and Animal Physiology; Hyperphagia; Immunohistochemistry; Insulin resistance; Internal Medicine; Keratins, Type I - analysis; Keratins, Type I - genetics; Ketogenic diet; Laboratories; Leerstoelgroep Fysiologie van mens en dier; Lipid metabolism; Lipid Metabolism - genetics; Lipids; Liver; Liver - chemistry; Liver - metabolism; Liver cancer; Liver diseases; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Metabolism; Molecular biology; Nutrition research; Obesity; Obesity - metabolism; original-article; Overweight; Physiological aspects; Public Health; Rats; Rats, Wistar; Risk; Risk factors; Transcriptome; Transcriptomes; Triglycerides; Up-Regulation; VLAG; WIAS
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2016.47

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.