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Title:Effects of weaning age and maternal nutrition on gene expression of longissimus muscle of beef steers
Author(s):Moisa, Sonia
Director of Research:Loor, Juan J.
Doctoral Committee Chair(s):Loor, Juan J.
Doctoral Committee Member(s):Drackley, James K.; Shike, Daniel W.; Pan, Yuan-Xiang
Department / Program:Animal Sciences
Discipline:Animal Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Marbling
Early weaning
Fetal programming
Transcriptomics
Adipogenesis
Beef
Abstract:Adipogenic/lipogenic transcriptional networks regulating intramuscular fat (IMF) deposition in response weaning age and dietary starch level were studied. The longissimus muscle (LM) of beef steers on an early weaning (141 days age) plus high-starch diet (EWS) or a normal weaning (NW, 222 days age) plus starch creep-feed diet (CFS) was biopsied at 0 (EW), 25, 50, 96 (NW), 167, and 222 (pre-slaughter) days. Expression patterns of 35 target genes were studied. From NW through slaughter all steers received the same high-starch diet. In EWS steers the expression of PPARG, other adipogenic (CEBPA, ZFP423) and lipogenic (THRSP, SREBF1, INSIG1) activators, and several enzymes (FASN, SCD, ELOVL6, PCK1, DGAT2) that participate in the process of IMF increased gradually to a peak between 96 and 167 days on treatment. Steers in NW did not achieve similar expression levels even by 222 days on treatment, suggesting a blunted response even when fed a high-starch diet after weaning. In conclusion, high-starch feeding at an early age (EWS) triggers precocious and sustained adipogenesis resulting in greater marbling. In a following study, we wanted to test if the exposure to an increased maternal nutrition during late gestation might result in an early increase in the expression of genes and/or other changes due to epigenetic regulation that leads to adipogenesis and lipogenesis in the offspring’s LM. A microarray analysis was performed in LM samples of early (EW) and normal weaned (NW) Angus × Simmental calves born from cows that were grazing endophyte-infected tall fescue/red clover pastures with no supplement (low plane of nutrition (LPN)), or supplemented with 2.3 kg and 9.1 kg of dried distiller’s grains with solubles and soyhulls (70% DDGS/30% soyhulls) (medium and high plane of nutrition (MPN, HPN) respectively) during last 90 days of gestation, at three time points (78, 187 and 354 days of age). Bioinformatics analysis highlighted that offspring transcriptome did not respond markedly to cow plane of nutrition, resulting in only 13 differentially expressed genes (DEG). However, weaning age and a high-starch diet (EW steers) strongly impacted the transcriptome (DEG = 167), especially causing the activation of the lipogenic program. In addition, between 78 and 187 days of age, EW steers had an activation of the innate immune system due presumably to macrophage infiltration in intramuscular fat. Between 187 and 354 days of age (i.e. the fattening phase), NW steers had an activation of the lipogenic transcriptome machinery, while EW steers had a clear inhibition of the gene transcription machinery. The latter appears to have occurred through the epigenetic control of histone acetylases, which were down-regulated. Higher cow plane of nutrition alone affected 35 DEG in the LM of steers that underscored the presence of a mechanism of macrophage infiltration likely originating from localized oxidative stress as a result of increased levels of hypoplasia and hypertrophy in LM. In conclusion, transcriptome analysis suggests that a macrophage infiltration-related impairment of lipogenesis was produced in LPN steers (especially in EW-LPN steers that had low marbling scores) as a consequence of weaning age and cow plane of nutrition. Finally, gene expression changes without a change in DNA sequence was assessed, mainly focusing in non-coding microRNAs (miRNA) epigenetics control. Results showed that proadipogenic miRNAs were controlling metabolism of LM of NW-MPN steers between 78 and 187 days of age through activation of: a) miR-103 that inhibits CAV1 that destabilizes INSR increasing insulin resistance, b) miR-143 that inhibits DLK1 that inhibits adipocyte differentiation through ERK1/2 activation, c) miR-21 that impaired TGFBR2-induced inhibition of adipocyte differentiation and seems to be related to serum adiponectin concentration. Furthermore, from the selected antiadipogenic miRNAs, cow plane of nutrition impaired miR-34a expression in MPN steers at 78 days of age. MiR-34a has a role on the activation of cell cycle arrest in LM by suppressing SIRT1, which leads to an activation of TP53 between 78 and 187 days of age. In conclusion, in MPN steers, inhibition of miR-34a expression at 78 days of age was the clearest sign of epigenetic regulation of LM of beef offspring due to cow plane of nutrition during late gestation.
Issue Date:2015-03-19
Type:Thesis
URI:http://hdl.handle.net/2142/78335
Rights Information:Copyright 2015 Sonia Moisa
Date Available in IDEALS:2015-07-22
Date Deposited:May 2015


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