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Metabolites
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Effects of Stress on Animal Metabolism
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Effects of Stress on Animal Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Animal Metabolism".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 5632

Special Issue Editors

Prof. Dr. Krystyna Pierzchala-Koziec

E-Mail Website
Guest Editor
Department of Animal Physiology, Faculty of Animal Sciences, University of Agriculture in Krakow, 30-059 Krakow, Poland
Interests: physiology; endocrinology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Colin Scanes

E-Mail Website
Guest Editor
Department of Biological Science, University of Wisconsin Milwaukee, Milwaukee, WI 53201-0413, USA
Interests: physiology; endocrinology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Within the simple but profound pioneering concept of stress advanced by Hans Selye, this Special Issue will explore the different responses of animals to individual stresses, looking at multiple categories of stressors, including the following:

  • Physical stressors, e.g., injury followed by healing, low or high temperatures, lack of water, and either insufficient or excess sodium;
  • Nutritional stresses, encompassing deficiencies in energy and specific nutrients;
  • Metabolic stressors, such as type 1 and 2 diabetes;
  • Pathogens as stressors;
  • Environmental toxicants as stressors;
  • Oxidative stresses;
  • Psychological stressors that impair welfare.

Responses to stressors can include the activation of the following:

  • The hypothalamus–pituitary–adrenal cortical axis, with cortisol as the major glucocorticoid in mammalian livestock and corticosterone as the major glucocorticoid in poultry and rodents;
  • Met-enkephalin and other opioid peptides;
  • The adrenal medulla, releasing epinephrine and/or norepinephrine;
  • Other stress-related hormones: growth hormone, prolactin, and ghrelin;
  • Protective responses to oxidative stresses;
  • Inflammatory cytokines.

This Special Issue, “Effects of Stress on Animal Metabolism”, will focus on these effects in domesticated animals but will not only include animal models and evolutionary considerations. Rather, it is anticipated that this Special Issue will also feature work from researchers in multiple fields, including physiology, nutrition, immunology, animal and poultry science, and veterinary medicine.

Prof. Dr. Krystyna Pierzchala-Koziec
Prof. Dr. Colin Scanes
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stressors
  • ACTH
  • glucocorticoids
  • mineralocorticoids
  • opioids
  • glycemia
  • growth
  • development
  • lactation
  • pregnancy

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

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24 pages, 5269 KB  
Article
The Metabolic Signatures Associated with the Effects of Aerobic Exercise on Depressive-like Behaviors in CUMS Rats
by Huan Xiang, Danhui Zhang, Yuchen Zhu, Jiangtao Hou and Yumei Han
Metabolites 2026, 16(2), 114; https://doi.org/10.3390/metabo16020114 - 5 Feb 2026
Viewed by 632
Abstract
Objectives: This study explored the antidepressant mechanisms of aerobic exercise in CUMS rats by analyzing urinary metabolomics (LC-MS and NMR), with the aim of providing both theoretical and practical support for exercise-based depression interventions. Methods: (1) Thirty-two Sprague-Dawley rats were acclimatized [...] Read more.
Objectives: This study explored the antidepressant mechanisms of aerobic exercise in CUMS rats by analyzing urinary metabolomics (LC-MS and NMR), with the aim of providing both theoretical and practical support for exercise-based depression interventions. Methods: (1) Thirty-two Sprague-Dawley rats were acclimatized for one week and then randomly assigned to four groups (n = 8 per group): control (C), control + aerobic exercise group (E), CUMS model (D), and CUMS + exercise (DE). Groups D and DE were subjected to nine types of CUMS stimuli. Behavioral indicators were assessed weekly, and the successful establishment of the CUMS model was confirmed at week 3. Following successful modeling, rats in groups E and DE underwent four weeks of aerobic exercise training. Throughout this period, groups D and DE continued to receive CUMS exposure, while groups C and E were maintained under standard control conditions. (2) At the end of week 7, behavioral tests were repeated. Twelve-hour urine samples were collected for metabolomic analysis using liquid chromatography–mass spectrometry (LC-MS) and 1H-NMR spectroscopy. The following morning, rats were euthanized under anesthesia. Whole blood was collected from the abdominal aorta, and serum was separated for subsequent biochemical assays. Bioinformatics approaches were employed to identify potential targets and signaling pathways associated with the antidepressant effects of aerobic exercise. (3) For statistical analysis, one-way or two-way analysis of variance (ANOVA) was applied to behavioral, physiological, and biochemical data, whereas multivariate statistical analysis was used for metabolomic data. Results: (1) By week 3, body mass, sucrose preference, rearing frequency, and the number of grid crossings were significantly lower in groups D and DE than in groups C and E (p < 0.05 or p < 0.01). These findings confirmed the successful establishment of the depression model. At week 7, all behavioral indicators in group DE showed significant recovery relative to group D (p < 0.05 or p < 0.01). (2) Compared with group C, corticosterone and blood ammonia levels were significantly elevated in group D (p < 0.01). In contrast, these levels were markedly reduced in group DE compared with group D (p < 0.01). (3) LC-MS analysis identified 25 urinary metabolites associated with depression in group D relative to group C. Among these, 21 were significantly downregulated and 4 were upregulated (p < 0.05 or p < 0.01), involving seven metabolic pathways. Following aerobic exercise intervention, six of these depression-related metabolites in group DE showed significant recovery (p < 0.05 or p < 0.01), which were associated with two metabolic pathways. (4) Integrated analysis of LC-MS and 1H-NMR data revealed glutamine as a common differential metabolite, linked to three metabolic pathways. All metabolic pathways modulated by aerobic exercise were related to amino acid metabolism. (5) Bioinformatics analysis indicated that AKT1, MTOR, IL6, RAF1, and TNF were core targets through which aerobic exercise regulated urinary metabolism in CUMS rats. Conclusions: A four-week regimen of aerobic exercise significantly improved depressive-like behaviors and enhanced anti-fatigue capacity in CUMS rats. This exercise regimen promoted urinary metabolic remodeling, primarily through the modulation of amino acid metabolism. Furthermore, its antidepressant effect is likely mediated through the regulation of core tissue targets—including AKT1, mTOR, IL-6, RAF1, and TNF—thereby influencing key pathways such as PI3K-AKT, MAPK/ERK, and neuroinflammatory signaling. Full article
(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)
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15 pages, 1462 KB  
Article
Metabolic Shifts Induced by Treatment with Statin Influences Circulating Concentrations of the Stress Hormone, Cortisol, but Has Different Effects on Selected Cytokines, Adipokines and Neuropeptides in Lean and Fat Lines of Young Pigs
by Krystyna Pierzchała-Koziec, Colin G. Scanes, Joanna Zubel-Łojek and Mirosław Kucharski
Metabolites 2025, 15(12), 797; https://doi.org/10.3390/metabo15120797 - 16 Dec 2025
Viewed by 619
Abstract
Background: It was hypothesized that short statin treatment would shift adipose expression, plasma and adipose tissue concentrations of adipokines and cytokines. Methods: Effects of a statin administration on adipokines (leptin, resistin and visfatin), adipose inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis [...] Read more.
Background: It was hypothesized that short statin treatment would shift adipose expression, plasma and adipose tissue concentrations of adipokines and cytokines. Methods: Effects of a statin administration on adipokines (leptin, resistin and visfatin), adipose inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factorα (TNFα)] were examined in young pigs of both lean and fat breeds. Results: Expression of resistin was increased while that of visfatin was decreased in visceral adipose tissue and, to a lesser extent, in epicardial adipose tissue. In young pigs treated with statin, there were increases in the plasma concentrations of leptin, resistin and TNFα. There were also decreases in the plasma concentrations of visfatin, cortisol, Met-enkephalin and endothelin-1. Concentrations of leptin in both epicardial and visceral adipose tissue were reduced in statin-treated pigs. There were marked differences between the epicardial and visceral adipose tissue. Concentrations of leptin were reduced with statin treatment in visceral adipose tissue irrespective of whether they were lean or fat breeds of pigs. Statin treatment was associated with increased concentrations of TNFα in epicardial adipose tissue and of IL-6 in visceral adipose tissue in both lean and fat breeds of pigs. Conclusions: It is concluded that statins cause shifts in the expression and/or concentrations of both adipokines and inflammatory cytokines in adipose tissue. Full article
(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)
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16 pages, 8671 KB  
Article
Excessive Iron Induces Macrophage Dysfunction in the Liver, Causing Adverse Pregnancy Outcomes in Mice
by Sayaka Shimazaki, Ren Ozawa, Akari Isobe, Sohei Kuribayashi, Hisataka Iwata and Koumei Shirasuna
Metabolites 2025, 15(7), 431; https://doi.org/10.3390/metabo15070431 - 24 Jun 2025
Viewed by 1123
Abstract
Background: Iron is an important micronutrient under physiological conditions, including pregnancy. On the other hand, excessive iron intake is also associated with adverse pregnancy outcomes. Macrophages are crucial in regulating iron homeostasis and pregnancy conditions. However, the role of macrophages in iron metabolism [...] Read more.
Background: Iron is an important micronutrient under physiological conditions, including pregnancy. On the other hand, excessive iron intake is also associated with adverse pregnancy outcomes. Macrophages are crucial in regulating iron homeostasis and pregnancy conditions. However, the role of macrophages in iron metabolism during pregnancy is unclear. Therefore, we used mouse models to investigate whether maternal iron overload induces pregnancy complications and their interactions with macrophages. Methods and Results: Administration of high-dose iron (iron dextran) by intraperitoneal injection to pregnant mice induced pregnancy complications such as fetal death, but low-dose iron did not affect fetal weight. In the placenta, the amount of iron was significantly increased and levels of macrophages were decreased by iron administration. In the liver, iron administration dramatically increased the amount of iron, with increased inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6. Macrophages were observed to surround deposited iron in the liver. In an in vitro experiment, treatment with iron stimulated TNFα secretion with cell death in macrophages, but not in liver cells. To investigate the importance of macrophages during pregnancy, clodronate liposomes were administered to reduce macrophages in pregnant mice. The macrophage reduction in pregnant mice resulted in an increased absorption rate and fetal growth restriction, together with higher iron accumulation and inflammatory cytokines in the liver. Conclusions: Maternal excess iron may induce inflammatory conditions with macrophage dysfunction in the liver, resulting in pregnancy complications. The reduction in macrophages also induced higher iron levels and adverse effects during pregnancy, suggesting a vicious cycle between excessive iron and macrophage dysfunction during pregnancy. Full article
(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)
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17 pages, 3290 KB  
Article
An Integrated Analysis of Transcriptomic and Metabolomic Effects Reveals Insights into Stress Responses in Largemouth Bass (Micropterus salmoides) Under MS-222 (Tricaine Methanesulfonate) Exposure
by Ping Gao, Rimeng Chen, Deyun Ma, Shanshan Lin, Haodong Yu and Xuezhen Zhang
Metabolites 2025, 15(6), 349; https://doi.org/10.3390/metabo15060349 - 23 May 2025
Cited by 3 | Viewed by 1277
Abstract
Background/Objectives: MS-222 is a commonly used anesthetic for fish. Research on the anesthetic mechanism of MS-222 is scarce, especially in largemouth bass. Therefore, this study investigated the tissue-specific transcriptomic and metabolomic effects of MS-222 anesthesia on largemouth bass (Micropterus salmoides). Methods: [...] Read more.
Background/Objectives: MS-222 is a commonly used anesthetic for fish. Research on the anesthetic mechanism of MS-222 is scarce, especially in largemouth bass. Therefore, this study investigated the tissue-specific transcriptomic and metabolomic effects of MS-222 anesthesia on largemouth bass (Micropterus salmoides). Methods: Experimental groups exposed to 40 mg/L MS-222 for 12 h were compared with untreated controls, and then transcriptomic and metabolomic analyses were performed on gill and liver samples. Results: Gill tissues exhibited 3252 differentially expressed genes (DEGs; 2309 upregulated and 943 downregulated) enriched in cardiac muscle contraction, cytoskeletal regulation, glycolysis, and toll-like receptor pathways for anesthetic adaptation. In contrast, liver tissues showed fewer DEGs (1140; 654 upregulated and 486 downregulated) primarily linked to metabolic network reorganization such as endoplasmic reticulum protein processing, PPAR signaling, and ribosome biogenesis. Metabolomic profiling demonstrated inverse patterns, with 173 differential metabolites in gills versus 297 in liver samples. Methyl nicotinate and N-acetyl-L-phenylalanine were the most significantly upregulated in the gill and liver samples. Metabolic pathway enrichment analysis revealed that MS-222-induced differential metabolites in the gill and liver of largemouth bass were predominantly associated with pathways involved in amino acid, fatty acid, phenylalanine, and nucleotide metabolism. Conclusions: These findings reveal that MS-222 anesthesia triggers organ-specific physiological adaptations through the differential regulation of metabolic and immune pathways, which provide multi-omics insights into the mechanistic basis of anesthetic responses in fish, highlighting distinct tissue strategies for managing chemical stress. Full article
(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)
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16 pages, 1293 KB  
Article
Comprehensive Characterization of Serum Lipids of Dairy Cows: Effects of Negative Energy Balance on Lipid Remodelling
by Zhiqian Liu, Wenjiao Wang, Joanne E. Hemsworth, Coralie M. Reich, Carolyn R. Bath, Monique J. Berkhout, Muhammad S. Tahir, Vilnis Ezernieks, Leah C. Marett, Amanda J. Chamberlain, Mike E. Goddard and Simone J. Rochfort
Metabolites 2025, 15(4), 274; https://doi.org/10.3390/metabo15040274 - 15 Apr 2025
Cited by 5 | Viewed by 1448
Abstract
Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the [...] Read more.
Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the transition period is only partially understood. Methods: Using a combination of reversed-phase liquid chromatography-mass spectrometry (RP-LC-MS), hydrophilic interaction-mass spectrometry (HILIC-MS), and lipid annotation software, we performed a comprehensive identification and quantification of serum of dairy cows in pasture-based Holstein-Friesian cows. The lipid remodelling induced by negative energy balance was investigated by comparing the levels of all identified lipids between the fresh lactation (5–14 days in milk, DIM) and full lactation (65–80 DIM) stages. Results: We identified 535 lipid molecular species belonging to 19 classes. The most abundant lipid class was cholesteryl ester (CE), followed by phosphatidylcholine (PC), sphingomyelin (SM), and free fatty acid (FFA), whereas the least abundant lipids included phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), acylcarnitine (AcylCar), ceramide (Cer), glucosylceramide (GluCer), and lactosylceramide (LacCer). Conclusions: A remarkable increase in most lipids and a dramatic decrease in FFAs, AcylCar, and DHA-containing species were observed at the full lactation compared to fresh lactation stage. Several serum lipid biomarkers for detecting negative energy balance in cows were also identified. Full article
(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)
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