Dataset Information

Integrated metabolomics and proteomics dynamics of serum samples reveals dietary Zeolite clinoptilolite supplementation restores energy balance in high yielding dairy cows

ABSTRACT: Dairy cows can suffer from a negative energy balance (NEB) during their transition from dry period to early lactation when feed intake does not sufficiently meet the energy requirements for body maintenance and homeostasis. The subsequent metabolic changes can increase the risk of postpartum diseases such as clinical ketosis, mastitis and fatty liver. Zeolite clinoptilolite (CPL), due to its ion-exchange property, has been often used to treat NEB and other disorders such as rumen digestion in animals in farming. However, limited information is available on the dynamics of global metabolomics and proteomic profiles in serum that could give us a better understanding on the associated altered biological pathways in response to CPL. Thus, in the present study, a total 64 cows randomly assigned to two groups: control (n=32) and CPL-treated (n=32) at time points of 30 days (n=8) and 10 days (n=8) prepartum stage and 5 days (n=8) and 26 (n=8) days postpartum stage. Labelled proteomics and untargeted metabolomics were performed following the determination of β-hydroxy-butyric acid (BHB) concentration in the samples indicating NEB. A total of 64 proteins were differentially expressed with a significant cohort appearing to play key roles in restoring the EB after CPL supplementation. In addition, 21 differentially expressed metabolites were chosen of 83 identified metabolites based on their high correlation with BHB. Joint pathway and interaction analysis revealed cross-talks among potential candidates such as valproic acid, leucic acid, glycerol, fibronectin and kinninogen-1 which could be responsible for restoring associated complications of NEB such as infertility or infection like mastitis. By using global proteomics and metabolomics strategy, the present study concluded that the CPL supplementation could lower NEB and restore energy balance in just a few weeks and explained the possible underlying pathways employed by the CPL.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Blood Serum

SUBMITTER: Sudipa Maity

LAB HEAD: Vladimir Mrljak

PROVIDER: PXD027551 | Pride | 2022-02-17

REPOSITORIES: Pride

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Integrated Metabolomics and Proteomics Dynamics of Serum Samples Reveals Dietary Zeolite Clinoptilolite Supplementation Restores Energy Balance in High Yielding Dairy Cows.

Maity Sudipa S Rubić Ivana I Kuleš Josipa J Horvatić Anita A Đuričić Dražen D Samardžija Marko M Ljubić Blanka Beer BB Turk Romana R Gračner Damjan D Maćešić Nino N Valpotić Hrvoje H Mrljak Vladimir V

Metabolites 20211205 12

Dairy cows can suffer from a negative energy balance (NEB) during their transition from the dry period to early lactation, which can increase the risk of postpartum diseases such as clinical ketosis, mastitis, and fatty liver. Zeolite clinoptilolite (CPL), due to its ion-exchange property, has often been used to treat NEB in animals. However, limited information is available on the dynamics of global metabolomics and proteomic profiles in serum that could provide a better understanding of the as ...[more]

PMID: 34940600

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Project description:Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and -hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affymetrix oligonucleotide array was used to determine global gene expression in the spleen of dairy cows in the early postpartum period. Spleen tissue was removed post mortem from five severe NEB (SNEB) and five medium NEB (MNEB) cows 15 days postpartum.SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals. A total of 545 genes were altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN- ; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity. Multiparous Holstein-Friesian cows (n=24) were blocked 2 weeks prior to expected calving date according to parity, body condition score, and previous lactation yield (average lactation 6477M-BM-1354kg) and randomly allocated to mild (MNEB; n=12) or severe (SNEB; n=12) NEB groups. MNEB cows were fed ad lib grass silage and 8 kg day-1 concentrates and milked once daily; SNEB cows were fed 25 kg day-1 silage and 4kg day-1 concentrate and milked three times daily. Measurements of body condition score and EB were used to select cows which showed extremes in EB from each group (MNEB, n=5; SNEB, n=5). Cows were slaughtered on days 6-7 of the first follicular wave after calving (mean number of days post-partum: MNEB mean 13.6 M-BM-1 0.75, range 11M-bM-^@M-^S15; SNEB mean 14.3 M-BM-1 0.56, range 13M-bM-^@M-^S16), based on daily transrectal ultrasonography.At slaughter the entire spleen was removed and weighed, and samples weighing 1 g were dissected, rinsed in RNase-free phosphate buffer, snap frozen in liquid nitrogen, stored for 4 h in dry ice, and subsequently stored at 80M-BM-0C.

Project description:The interplay between pathogens and hosts has been studied for decades using targeted approaches such as the analysis of mutants and host immunological responses. Although much has been learned from such studies, they focus on individual pathways and fail to reveal the global effects of infection on the host. To alleviate this issue, high-throughput methods such as transcriptomics and proteomics have been used to study host-pathogen interactions. Recently, metabolomics was established as a new method to study changes in the biochemical composition of host tissues. We report a metabolomics study of Salmonella enterica serovar Typhimurium infection. We used Fourier Transform Ion Cyclotron Resonance Mass Spectrometry with Direct Infusion to reveal that dozens of host metabolic pathways are affected by Salmonella in a murine infection model. In particular, multiple host hormone pathways are disrupted. Our results identify unappreciated effects of infection on host metabolism and shed light on mechanisms used by Salmonella to cause disease, and by the host to counter infection. Female C57BL/6 mice were infected with Salmonella enterica serovar Typhimurium SL1344 cells by oral gavage. Feces and livers were collected and metabolites extracted using acetonitrile. For experiments with feces, samples were collected from 4 mice before and after infection. For liver experiments, 11 uninfected and 11 infected mice were used. Samples were combined into 3 groups of 3-4 mice each, resulting in the analysis of 3 group samples of uninfected and 3 of infected mice. Extracts were infused into a 12-T Apex-Qe hybrid quadrupole-FT-ICR mass spectrometer equipped with an Apollo II electrospray ionization source, a quadrupole mass filter and a hexapole collision cell. Raw mass spectrometry data were processed as described elsewhere (Han et al. 2008. Metabolomics. 4:128-140 [PMID 19081807]). To identify differences in metabolite composition between uninfected and infected samples, we filtered the list of masses for metabolites which were present on one set of samples but not the other. Additionally, we calculated the ratios between averaged intensities of metabolites from uninfected and infected mice. To assign possible metabolite identities, monoisotopic neutral masses of interest were queried against MassTrix (http://masstrix.org). Masses were searched against the Mus musculus database within a mass error of 3 ppm. Data were analyzed by unpaired t tests with 95% confidence intervals.

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	TMTsix10_cow.raw	Raw
	TMTsix11_cow.raw	Raw
	TMTsix12_cow.raw	Raw
	TMTsix13_cow.raw	Raw
	TMTsix1_cow.msf	Msf