Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data

Pedroso, Amanda Paula; Souza, Adriana Pereira de; Dornellas, Ana Paula Segantine; Oyama, Lila Missae; Nascimento, Cláudia Maria Oller do; Santos, Gianni Mara Silva dos; Rosa, José César; Bertolla, Ricardo Pimenta; Klawitter, Jelena; Christians, Uwe; Ribeiro, Eliane

doi:10.1021/acs.jproteome.6b00923

Cited by 38 publications

(36 citation statements)

References 62 publications

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“…It is one of the rare studies to have compared the metabolomes of non-nervous and nervous system tissues, including one protected by a partial blood-brain barrier, and the first to have investigated the continuum between the HYP and the WOB in terms of their modulation by metabolic imbalance. Nervous tissues metabolomes have been poorly explored in a DOHaD context, mostly in cases of maternal intra-uterine malnutrition [38,39] or under-restriction [22], only one was dedicated to the effect of maternal obesity, but focused on fatty acids profile [23], and none explored the WOB, despite its unique metabolic network architecture and its importance as a metabolic sensor controlling food intake [40].…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes

et al. 2020

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Nutritional changes during developmental windows are of particular concern in offspring metabolic disease. Questions are emerging concerning the role of maternal weight changes before conception, particularly for weight loss, in the development of diet-related disorders. Understanding the physiological pathways affected by the maternal trajectories in the offspring is therefore essential, but a broad overview is still lacking. We recently reported both metabolic and behavioral negative outcomes in offspring born to obese or weight-loss mothers and fed a control of high-fat diet, suggesting long-term modeling of metabolic pathways needing to be further characterized. Using non-targeted LC–HRMS, we investigated the impact of maternal and post-weaning metabolic status on the adult male offspring’s metabolome in three tissues involved in energy homeostasis: liver, hypothalamus and olfactory bulb. We showed that post-weaning diet interfered with the abundance of several metabolites, including 1,5-anhydroglucitol, saccharopine and β-hydroxybutyrate, differential in the three tissues. Moreover, maternal diet had a unique impact on the abundance of two metabolites in the liver. Particularly, anserine abundance, lowered by maternal obesity, was normalized by a preconceptional weight loss, whatever the post-weaning diet. This study is the first to identify a programming long-term effect of maternal preconception obesity on the offspring metabolome.

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Section: Discussionmentioning

confidence: 99%

Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes

et al. 2020

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“…Data were acquired in the data independent acquisition mode HDMS E with ion mobility separation in the m/z range of 50-2,000 and in the resolution mode. Peptide ions were fragmented by collision induced dissociation (CID) and energies were alternated between 4 eV and a ramp of 15-65 eV for precursor ion and fragment ions, respectively, using scan times of 1.25 s (Abreu et al, 2017;Pedroso et al, 2017). The ESI source was operated in positive mode with a capillary voltage of 3.0 kV, block temperature of 100°C, and cone voltage of 40 V. For lock mass correction, Glu-Fibrinopeptide B (500 fmol/mL in 50% acetonitrile, 0.1% formic acid; Peptide 2.0) was infused through the reference sprayer at 500 nl/min and sampled for 0.5 s every 60 s. The venom pool was analyzed in triplicate.…”

Section: Mass Spectrometry: Proteomicsmentioning

confidence: 99%

A Multiomics Approach Unravels New Toxins With Possible In Silico Antimicrobial, Antiviral, and Antitumoral Activities in the Venom of Acanthoscurria rondoniae

et al. 2020

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The Araneae order is considered one of the most successful groups among venomous animals in the world. An important factor for this success is the production of venoms, a refined biological fluid rich in proteins, short peptides and cysteine-rich peptides (CRPs). These toxins may present pharmacologically relevant biological actions, as antimicrobial, antiviral and anticancer activities, for instance. Therefore, there is an increasing interest in the exploration of venom toxins for therapeutic reasons, such as drug development. However, the process of peptide sequencing and mainly the evaluation of potential biological activities of these peptides are laborious, considering the low yield of venom extraction and the high variability of toxins present in spider venoms. Here we show a robust methodology for identification, sequencing, and initial screening of potential bioactive peptides found in the venom of Acanthoscurria rondoniae. This methodology consists in a multiomics approach involving proteomics, peptidomics and transcriptomics analyses allied to in silico predictions of antibacterial, antifungal, antiviral, and anticancer activities. Through the application of this strategy, a total of 92,889 venom gland transcripts were assembled and 84 novel toxins were identified at the protein level, including seven short peptides and 10 fully sequenced CRPs (belonging to seven toxin families). In silico analysis suggests that seven CRPs families may have potential antimicrobial or antiviral activities, while two CRPs and four short peptides are potentially anticancer. Taken together, our results demonstrate an effective multiomics strategy for the discovery of new toxins and in silico screening of potential bioactivities. This strategy may be useful in toxin discovery, as well as in the screening of possible activities for the vast diversity of molecules produced by venomous animals.

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“…Peptides were then eluted onto an analytical C18 column (nanoAcquity BEH 75 μm × 200 mm, 1.7 m) at a flow rate of 275 nL/min, using a gradient of 7-35% of phase B (0.1% formic acid in acetonitrile) in 90 min. Data were acquired in the in data-independent mode UDMSE [42] in the m/z range of 50-2000 and in resolution mode. Collision energies were alternated between 4 eV and a ramp of 17-60 eV for precursor ion and fragment ions, respectively, using scan times of 1.25 s. The ESI source was operated in positive mode with a capillary voltage of 3.0 kV, block temperature of 70 °C, and cone voltage of 40 V. For lock mass correction, [Glu1]-Fibrinopeptide B solution (500 fmol/mL in 50% acetonitrile, 0.1% formic acid; Peptide 2.0) was infused through the reference sprayer at 500 nL/min and sampled for 0.5 s at each 60 s.…”

Section: Protein Identification By Mass Spectrometrymentioning

confidence: 99%

Venom complexity of Bothrops atrox (common lancehead) siblings

Hatakeyama

Tasima

Bravo-Tobar

et al. 2020

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Variability in snake venoms is a well-studied phenomenon. However, sex-based variation of Bothrops atrox snake venom using siblings is poorly investigated. Bothrops atrox is responsible for the majority of snakebite accidents in the Brazilian Amazon region. Differences in the venom composition of Bothrops genus have been linked to several factors such as ontogeny, geographical distribution, prey preferences and sex. Thus, in the current study, venom samples of Bothrops atrox male and female siblings were analyzed in order to compare their biochemical and biological characteristics. Methods: Venoms were collected from five females and four males born from a snake captured from the wild in São Bento (Maranhão, Brazil), and kept in the Laboratory of Herpetology of Butantan Intitute. The venoms were analyzed individually and as a pool of each gender. The assays consisted in protein quantification, 1-DE, mass spectrometry, proteolytic, phospholipase A 2 , L-amino acid oxidase activities, minimum coagulant dose upon plasma, minimum hemorrhagic dose and lethal dose 50%. Results: Electrophoretic profiles of male's and female's venom pools were quite similar, with minor sex-based variation. Male venom showed higher LAAO, PLA 2 and hemorrhagic activities, while female venom showed higher coagulant activity. On the other hand, the proteolytic activities did not show statistical differences between pools, although some individual variations were observed. Meanwhile, proteomic profile revealed 112 different protein compounds; of which 105 were common proteins of female's and male's venom pools and seven were unique to females. Despite individual variations, lethality of both pools showed similar values. Conclusion: Although differences between female and male venoms were observed, our results show that individual variations are significant even between siblings, highlighting that biological activities of venoms and its composition are influenced by other factors beyond gender.

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Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data

Cited by 38 publications

References 62 publications

Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes

Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes

A Multiomics Approach Unravels New Toxins With Possible In Silico Antimicrobial, Antiviral, and Antitumoral Activities in the Venom of Acanthoscurria rondoniae

Venom complexity of Bothrops atrox (common lancehead) siblings

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