title: Seasonal heat stress affects adipose tissue proteome toward enrichment of the Nrf2-mediated oxidative stress response in late-pregnant dairy cows.
abstract: Environmental heat stress and metabolic stress during transition from late gestation to lactation are main factors limiting production in dairy cattle, and there is a complex interaction between them. Many proteins expressed in adipose tissue are involved in metabolic responses to stress. We aimed to investigate the effects of seasonal heat stress on adipose proteome in late-pregnant cows, and to identify biomarkers of heat stress. Late pregnant cows during summer heat stress (S, n=18), or during the winter season (W, n=12) were used. Subcutaneous adipose tissue biopsies sampled 14days prepartum from S (n=10) and W (n=8) were analyzed by intensity-based, label-free, quantitative shotgun proteomics (nano-LC-MS/MS). Plasma concentrations of malondialdehyde and cortisol were higher in S than in W cows. Proteomic analysis revealed that 107/1495 proteins were differentially abundant in S compared to W (P<0.05 and fold change of at least ±1.5). Top canonical pathways in S vs. W adipose were Nrf2-mediated oxidative stress response, acute-phase response, and FXR/RXR and LXR/RXR activation. Novel biomarkers of heat stress in adipose tissue were found. These findings indicate that seasonal heat stress has a unique effect on adipose tissue in late-pregnant cows.
  
  
  
  This work shows that seasonal heat stress increases plasma concentrations of the oxidative stress marker malondialdehyde and cortisol in transition dairy cows. As many proteins expressed in the adipose tissue are involved in metabolic responses to stress, we investigated the effects of heat stress on the proteome of adipose tissue from late-pregnant cows during summer or winter seasons. We demonstrated that heat stress enriches several stress-related pathways, such as the Nrf2-mediated oxidative stress response and the acute-phase response in adipose tissues. Thus, environmental heat stress has a unique effect on adipose tissue in late-pregnant cows, as part of the regulatory adaptations to chronic heat load during the summer season. In addition, this study presents the widest available dataset of adipose tissue proteome in dairy cows, and revealed several novel biomarkers of heat stress in adipose tissue of dairy cows, the use of which awaits further validation.
authors.affiliation: Department of Ruminant Science, Institute of Animal Sciences, Volcani Center, Rishon Lezion, Israel. Electronic address: mayak@volcani.agri.gov.il.
authors.forename: M
authors.initials: M
authors.lastname: Zachut
authors.affiliation: Department of Ruminant Science, Institute of Animal Sciences, Volcani Center, Rishon Lezion, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Kra
authors.affiliation: Department of Ruminant Science, Institute of Animal Sciences, Volcani Center, Rishon Lezion, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Livshitz
authors.affiliation: Department of Ruminant Science, Institute of Animal Sciences, Volcani Center, Rishon Lezion, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Portnick
authors.affiliation: Department of Ruminant Science, Institute of Animal Sciences, Volcani Center, Rishon Lezion, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Yakoby
authors.affiliation: The Ilana and Pascal Mantoux Institute for Bioinformatics, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Friedlander
authors.affiliation: de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Levin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D030562:Databases, Protein; D005260:Female; D018869:Heat-Shock Response / Q000502:physiology*; D011247:Pregnancy / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D012621:Seasons
chemical_list: D011257:Pregnancy Proteins; D020543:Proteome
keywords: Adipose; Dairy cow; Heat stress; Malondialdehyde; Nrf2; Proteomics