The previously reported genetic polymorphisms of the stearoyl-CoA desaturase (SCD1) and sterol regulatory element binding protein-1 (SREBP-1) genes were investigated in Fleckvieh bulls using the PCR-RFLP and AS-PCR methods, respectively. The genomic DNA was obtained from a total of 370 bulls. The frequencies of alleles A and V of the single nucleotide polymorphism in exon 5 of the SCD1 gene (SNP 878C>T) were 0.555 and 0.445, respectively. In the 84-bp Ins/Del polymorphism in intron 5 of the SREBP-1 gene, the frequency of the L allele (insertion) was markedly higher (0.920) than that of the S allele (deletion; 0.080). Fatty acid profile was determined in a total of 367 samples of muscle fat (MSF) and 150 samples of subcutaneous fat (SCF). The AA genotype of SCD1 polymorphism showed a lower content of C18:0 (P<0.01) and higher contents of C14:1 cis-9 (P<0.001) and C18:1 cis-9 (P<0.05) in MSF compared to the VV genotype. As a result, the bulls with genotypes AA or AV had lower SFA (P<0.01), higher MUFA (P<0.05) and higher MUFA/SFA (P<0.01) than VV animals. The results obtained for SCF were similar. The SREBP-1 polymorphism was associated with a higher content of C14:1 cis-9 (P<0.01) in the LS compared to LL genotype in SCF. The results of this study demonstrated the existence of the polymorphisms in the SCD1 and SREBP-1 genes in the population of Fleckvieh cattle and their associations with the concentrations of several MSF and SCF fatty acids.
- MeSH
- DNA analýza MeSH
- exony MeSH
- frekvence genu MeSH
- genom MeSH
- genotyp MeSH
- introny MeSH
- jednonukleotidový polymorfismus * MeSH
- kosterní svaly chemie MeSH
- kyseliny mastné mononenasycené analýza MeSH
- mastné kyseliny analýza genetika MeSH
- podkožní tuk chemie MeSH
- polymerázová řetězová reakce metody MeSH
- protein SREBP1 genetika MeSH
- skot MeSH
- stearyl-CoA-desaturasa genetika MeSH
- uhlík MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- kyseliny mastné mononenasycené MeSH
- mastné kyseliny MeSH
- protein SREBP1 MeSH
- stearyl-CoA-desaturasa MeSH
- uhlík MeSH
The temporal relationship of hepatic steatosis and changes in liver oxidative stress and fatty acid (FA) composition to the development of non-alcoholic steatohepatitis (NASH) remain to be clearly defined. Recently, we developed an experimental model of hepatic steatosis and NASH, the transgenic spontaneously hypertensive rat (SHR) that overexpresses a dominant positive form of the human SREBP-1a isoform in the liver. These rats are genetically predisposed to hepatic steatosis at a young age that ultimately progresses to NASH in older animals. Young transgenic SHR versus SHR controls exhibited simple hepatic steatosis which was associated with significantly increased hepatic levels of oxidative stress markers, conjugated dienes, and TBARS, with decreased levels of antioxidative enzymes and glutathione and lower concentrations of plasma alpha- and gamma-tocopherol. Transgenic rats exhibited increased plasma levels of saturated FA, decreased levels of n-3 and n-6 polyunsaturated FA (PUFA), and increased n-6/n-3 PUFA ratios. These results are consistent with the hypothesis that excess fat accumulation in the liver in association with increased oxidative stress and disturbances in the metabolism of saturated and unsaturated fatty acids may precede and contribute to the primary pathogenesis of NASH.
- MeSH
- genetická predispozice k nemoci MeSH
- játra metabolismus patologie MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- oxidační stres * MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- protein SREBP1 genetika metabolismus MeSH
- ztučnělá játra genetika metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- nenasycené mastné kyseliny MeSH
- protein SREBP1 MeSH
- SREBF1 protein, human MeSH Prohlížeč
Approximately 30% of patients with hypertension have hepatic steatosis, and it has recently been proposed that fatty liver be considered a feature of the metabolic syndrome. Obesity, diet, and level of physical activity are likely factors modulating risk for hepatic steatosis, however genetic factors could also influence susceptibility or resistance to fatty liver in hypertensive or normotensive subjects. In genetic studies in spontaneously hypertensive rats (SHRs) and Brown Norway (BN) rats, we discovered that a variant form of sterol regulatory element binding transcription factor 1 (Srebf1 gene, SREBP-1 protein) underlies a quantitative trait locus (QTL) influencing hepatic cholesterol levels in response to a high cholesterol diet. Compared with the BN allele of Srebf1, the SHR allele of Srebf1 includes variants in the promoter and coding regions that are linked to hepatic deficiency of SREBP-1 mRNA and protein, reduced expression of the SREBP-1 target gene stearoyl-CoA desaturase 1, reduced promoter activity for SREBP-1c, and relative protection from dietary induced accumulation of liver cholesterol. Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels, thereby confirming Srebf1 as a QTL influencing hepatic lipid metabolism in the rat. The Srebf1 variant regulating hepatic cholesterol did not appear to affect blood pressure. These findings (1) are consistent with the results of association studies indicating that common polymorphisms affecting SREBP-1 may influence cholesterol synthesis in humans and (2) indicate that variation in Srebf1 may influence risk for hepatic steatosis.
- MeSH
- alely MeSH
- cholesterol metabolismus MeSH
- geneticky modifikovaná zvířata MeSH
- hypertenze komplikace genetika MeSH
- játra metabolismus MeSH
- krevní tlak fyziologie MeSH
- krysa rodu Rattus MeSH
- lokus kvantitativního znaku genetika MeSH
- mutace genetika MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- protein SREBP1 genetika metabolismus MeSH
- rizikové faktory MeSH
- sekvenční analýza DNA MeSH
- ztučnělá játra komplikace genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- cholesterol MeSH
- protein SREBP1 MeSH
- Srebf1 protein, rat MeSH Prohlížeč
