Obesity resistant mechanisms in the Lean polygenic mouse model as indicated by liver transcriptome and expression of selected genes in skeletal muscle
| Autor: | Bart Staels, Peter Juvan, Gregor Fazarinc, Catherine Fievet, Damjana Rozman, Matjaž Simončič, Tadeja Režen, Simon Horvat |
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| Přispěvatelé: | BMC, Ed., University of Ljubljana, Institute of Anatomy, University of Ljubljana -Histology and Embryology-Veterinary Faculty, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE), National Institute of Chemistry, Biotechnical Faculty, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Předmět: |
Male
medicine.medical_specialty lcsh:QH426-470 medicine.drug_class lcsh:Biotechnology Quantitative Trait Loci Biology Transcriptome Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Thinness [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] lcsh:TP248.13-248.65 Internal medicine medicine Genetics Animals Obesity Muscle Skeletal Oligonucleotide Array Sequence Analysis 030304 developmental biology 2. Zero hunger 0303 health sciences Bile acid Reverse Transcriptase Polymerase Chain Reaction Cholesterol Gene Expression Profiling Reverse cholesterol transport Skeletal muscle Metabolism Gene expression profiling lcsh:Genetics Phenotype Endocrinology medicine.anatomical_structure Liver chemistry Biochemistry [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] CYP8B1 030217 neurology & neurosurgery Research Article Biotechnology |
| Zdroj: | BMC Genomics, Vol 12, Iss 1, p 96 (2011) BMC Genomics BMC Genomics, 2011, 12 (1), pp.96. ⟨10.1186/1471-2164-12-96⟩ BMC Genomics, BioMed Central, 2011, 12 (1), pp.96. ⟨10.1186/1471-2164-12-96⟩ |
| ISSN: | 1471-2164 |
| DOI: | 10.1186/1471-2164-12-96 |
| Popis: | Background Divergently selected Lean and Fat mouse lines represent unique models for a polygenic form of resistance and susceptibility to obesity development. Previous research on these lines focused mainly on obesity-susceptible factors in the Fat line. This study aimed to examine the molecular basis of obesity-resistant mechanisms in the Lean line by analyzing various fat depots and organs, the liver transcriptome of selected metabolic pathways, plasma and lipid homeostasis and expression of selected skeletal muscle genes. Results Expression profiling using our custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol biosynthesis genes compared to the Fat line, although this was not reflected in elevation of total plasma or liver cholesterol. However, FPLC analysis showed that protective HDL cholesterol was elevated in Lean mice. A significant difference between the strains was also found in bile acid metabolism. Lean mice had a higher expression of Cyp8b1, a regulatory enzyme of bile acid synthesis, and the Abcb11 bile acid transporter gene responsible for export of acids to the bile. Additionally, a higher content of blood circulating bile acids was observed in Lean mice. Elevated HDL and upregulation of some bile acids synthesis and transport genes suggests enhanced reverse cholesterol transport in the Lean line - the flux of cholesterol out of the body is higher which is compensated by upregulation of endogenous cholesterol biosynthesis. Increased skeletal muscle Il6 and Dio2 mRNA levels as well as increased activity of muscle succinic acid dehydrogenase (SDH) in the Lean mice demonstrates for the first time that changes in muscle energy metabolism play important role in the Lean line phenotype determination and corroborate our previous findings of increased physical activity and thermogenesis in this line. Finally, differential expression of Abcb11 and Dio2 identifies novel strong positional candidate genes as they map within the quantitative trait loci (QTL) regions detected previously in crosses between the Lean and Fat mice. Conclusion We identified novel candidate molecular targets and metabolic changes which can at least in part explain resistance to obesity development in the Lean line. The major difference between the Lean and Fat mice was in increased liver cholesterol biosynthesis gene mRNA expression, bile acid metabolism and changes in selected muscle genes' expression in the Lean line. The liver Abcb11 and muscle Dio2 were identified as novel positional candidate genes to explain part of the phenotypic difference between the Lean and Fat lines. |
| Databáze: | OpenAIRE |
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