Significant changes in hepatic transcriptome and circulating miRNAs are associated with diet‐induced metabolic syndrome in apoE3L.CETP mice

Autor: Dimitris Kardassis, Ioannis Evangelakos, Vasilis Nidris, Despoina Vassou, Dimitris Nasias, Erika Tarasco, Thomas A. Lutz
Přispěvatelé: University of Zurich, Kardassis, Dimitris
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Physiology
Clinical Biochemistry
1308 Clinical Biochemistry
Biology
Diet
High-Fat
metabolic syndrome
1307 Cell Biology
Transcriptome
Mice
transcriptomics
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Lipid droplet
Internal medicine
MetS
apoE3L.CETP mice
Gene expression
medicine
Animals
Circulating MicroRNA
Obesity
gene signatures
Diet
Fat-Restricted
microarrays
Gene Expression Profiling
1314 Physiology
Cell Biology
Gene signature
10081 Institute of Veterinary Physiology
medicine.disease
Dietary Fats
Fatty Liver
Disease Models
Animal
030104 developmental biology
Endocrinology
Liver
10076 Center for Integrative Human Physiology
030220 oncology & carcinogenesis
Humanized mouse
570 Life sciences
biology
Steatosis
Metabolic syndrome
Zdroj: Journal of Cellular Physiology. 234:20485-20500
ISSN: 1097-4652
0021-9541
DOI: 10.1002/jcp.28649
Popis: Long-term exposure to excess dietary fat leads to obesity and the metabolic syndrome (MetS). The purpose of the present study was to identify global changes in liver gene expression and circulating miRNAs in a humanized mouse model of diet-induced MetS. Male apoE3L.CETP mice received a high-fat diet (HFD) or a low-fat diet (LFD) for different time periods and the progression of MetS pathology was monitored. A separate group of mice was divided into responders (R) or nonresponders (NR) and received HFD for 16 weeks. We found that mice receiving the HFD developed manifestations of MetS and displayed an increasing number of differentially expressed transcripts at 4, 8, and 12 weeks compared with mice receiving the LFD. Significantly changed genes were functionally annotated to metabolic diseases and pathway analysis revealed the downregulation of genes in cholesterol and fatty acid biosynthesis and upregulation of genes related to lipid droplet formation, which was in line with the development of hepatic steatosis. In the serum of the apoE3L.CETP mice we identified three miRNAs that were upregulated specifically in the HFD group. We found that responder mice have a distinct gene signature that differentiates them from nonresponders. Comparison of the two diet intervention studies revealed a limited number of common differentially expressed genes but the expression of these common genes was affected in a similar way in both studies. In conclusion, the characteristic hepatic gene signatures and serum miRNAs identified in the present study provide novel insights to MetS pathology and could be exploited for diagnostic or therapeutic purposes.
Databáze: OpenAIRE
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