Laboratory Animal Research最新文献

{"title":"Comparative transcriptome analysis of PBMCs in cats diagnosed with and recovered from FIPV.","authors":"Ju Young Lee, Hyeong Ryeol Cho, Hong-Geun Oh, Jeong Ho Hwang","doi":"10.1186/s42826-025-00247-5","DOIUrl":"10.1186/s42826-025-00247-5","url":null,"abstract":"<p><strong>Background: </strong>Feline infectious peritonitis is a viral disease caused by feline coronavirus an enveloped virus with a single-stranded RNA genome that is approximately 30 kb long. Although FCoV generally causes mild symptoms, approximately 5% of cases progress to death in cats worldwide. FCoV shares certain virological features with severe acute respiratory syndrome coronavirus 2 that causes COVID-19, indicating that common therapeutic strategies may be applicable. GS-441524 the parent drug of remdesivir and a competitive inhibitor of nucleoside triphosphates in viral RNA synthesis is a well-known treatment for FIP. However, comparative transcriptome and gene ontology analyses of normal (Normal), FIP-diseased (FIPD), and FIP-recovered (FIPR) cats have not yet been conducted.</p><p><strong>Results: </strong>In this study, we compared the mRNA expression profiles of peripheral blood mononuclear cells from Normal, FIPD, and FIPR cats to identify immunological alterations. We identified 677 (FIPD/Normal) and 431 (FIPR/FIPD) differentially expressed genes with statistical significance. These data were input into the bioinformatics program. As a result, the analysis revealed statistically significant and contrasting patterns of canonical pathways of neutrophil degranulation and interleukin-8 (IL-8) signaling pathways. Additionally, we observed that kruppel-like factor 6 (KLF6) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were upstream molecules of IL-8, promoting neutrophil activation and function.</p><p><strong>Conclusions: </strong>This study identified immunological alterations in PBMCs of Normal, FIPD, and FIPR cats. KLF-6 and NF-κB were found to regulate IL-8-mediated neutrophil activation.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"18"},"PeriodicalIF":2.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxorubicin-mediated testicular toxicity is associated with dysregulated mTOR/Beclin-1 pathways, oxidative stress, inflammation and apoptosis in Wistar rats: preventive role of lutein.","authors":"Jennifer Efe Jaiyeoba-Ojigho, Jerome Ndudi Asiwe, Joseph Chimezie, Blessing Oluwakemi Abe, Oghenemarho Monalisa Ataikiru, Taniyohwo Mamerhi Enaohwo, Alexander Obidike Naiho, Lilian Ebele Chris-Ozoko, Godstime Jesukobiruo Ibada, Sylvester Ifeakachukwu Okuepusu, Favour Isioma Ikukaiwe, Winnie Taiye Ogwu","doi":"10.1186/s42826-025-00249-3","DOIUrl":"10.1186/s42826-025-00249-3","url":null,"abstract":"<p><strong>Background: </strong>Lutein offers undoubted hope for preventing doxorubicin uncharacteristic reproductive function which remains a worldwide health concern in cancer chemotherapy. However, the mechanisms underlying the effect of lutein on maintaining the male reproductive milieu have not yet been fully identified. The current study investigates the preventive effect of lutein in doxorubicin-induced testicular toxicity.</p><p><strong>Methods: </strong>Twenty male Wistar rats were randomly assigned into four groups of five animals (n = 5) and were pretreated with lutein (40 mg/kg i.p) prior to doxorubicin treatment (15 mg/kg i.p). Following the end of the experiment, animals were euthanized and the testes were collected and processed for semen and biochemical analysis.</p><p><strong>Results: </strong>The results revealed that exposure to doxorubicin caused hormonal imbalance, reduced semen quality and elicited oxidative stress, inflammatory reactions, apoptosis as well as dysregulation of autophagic process which was accompanied by fibrosis and histomorphological aberrations. Interestingly, pretreatment with lutein significantly restored hormonal balance and protected against the adverse effects of doxorubicin.</p><p><strong>Conclusions: </strong>The findings of this study showed that lutein prevents doxorubicin-mediated testicular toxicity via modulation autophagic pathways accompanied with inhibition of oxidative stress, inflammation and apoptosis.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"17"},"PeriodicalIF":2.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of H1N1 strain A/PR/8/34 influenza to build a mouse model of viral respiratory sepsis.","authors":"Yaqing Jiao, Yuee Cai, Yilin Zhang, Ka-Tim Choy, Ka-Man Cheng, John M Nicholls, Pui-Kin Lam, Hui-Ling Yen, Timothy H Rainer","doi":"10.1186/s42826-025-00248-4","DOIUrl":"10.1186/s42826-025-00248-4","url":null,"abstract":"<p><strong>Background: </strong>Community-acquired respiratory infections are a prevalent cause of sepsis. Current animal models simulate peritoneal rather than respiratory sepsis. This study sought to appraise an influenza model for its ability to develop sepsis.</p><p><strong>Methods: </strong>Twenty-four six-week-old male BALB/c mice were intranasally inoculated with H1N1 strain A/PR/8/34 virus at 3.7 × 10^- 1, 3.7 × 10⁰, 3.7 × 10¹, 3.7 × 10², 3.7 × 10³, 3.7 × 10⁴ median tissue culture infectious dose (TCID50) to acquire different levels of clinical severity. Murine Sepsis Score (MSS) was recorded daily over 14 days. Platelets, serum bilirubin and creatinine levels were measured to reflect coagulopathy, liver and renal dysfunction. These three parameters are from the Sequential Organ Failure Assessment (SOFA) score which is routinely used for monitoring human sepsis. The primary outcome is organ dysfunction.</p><p><strong>Results: </strong>Out of 24 infected mice, seven (29%) did not survive beyond 9 days. MSS predicted mortality with an AUC of 0.989 (95%CI: 0.978-1.000; P < 0.001). Liver and renal dysfunction were detected in one non-survived and six survived mice. Histological examination revealed inflammation in lung and liver but not kidney tissues.</p><p><strong>Conclusions: </strong>This study demonstrates the potential of influenza to cause organ dysfunction, providing a basis for building a murine model specific for viral respiratory sepsis, and more closely simulating human viral sepsis.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"16"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of commercial diets on fecal consistency and defecation frequency in rhesus macaques (Macaca mulatta) with chronic intermittent idiopathic diarrhea.","authors":"Annemiek Maaskant, Niels R Blees, Antoine Smits, Ronald J Corbee, Jaco Bakker, Jan A M Langermans, Edmond J Remarque","doi":"10.1186/s42826-025-00246-6","DOIUrl":"10.1186/s42826-025-00246-6","url":null,"abstract":"<p><strong>Background: </strong>Recurrent diarrhea is common health and welfare problem in captive rhesus macaques (Macaca mulatta). Aside from infectious causes, dietary factors have been implicated in diarrhea. Therefore, the main objective of this study was to evaluate commercially available pelleted diets in rhesus macaques with chronic intermittent idiopathic diarrhea. The main differences between these diets were lactose and fiber content. A randomized cross-over diet study was conducted to investigate the influence of each diet on fecal consistency and defecation frequency as indicators of diarrhea. Nine animals with chronic intermittent diarrhea and four controls were included. Each diet was fed for approximately three months, with a similar wash-out period after each diet cycle. The fecal consistency was graded using the Waltham Faeces Scoring system, with a cutoff score of > 3.5 indicating diarrhea. Both groups and diets were compared by both mixed and fixed effect models.</p><p><strong>Results: </strong>Descriptive data showed that the mean fecal consistency score was highest in the diarrhea group in the standard diet at 3.71 ± 0.456 whereas the lowest mean fecal consistency scores were observed for lactose-free and high fiber diet in both diarrhea (3.25 ± 0.423) and control group (3.04 ± 0.346). A significant improvement of the fecal consistency score was detected in the diarrhea group when fed lactose-free diets (-0.41(-0.65 - -0.16, P < 0.01) and -0.47(-0.68 --0.25, P < 0.0002), respectively). Lactose-free and high fiber content showed the best outcome regarding improvement of the fecal consistency score -0.47(CL -0.68-- 0.25, P < 0.0002). Defecation frequency increased in both groups with 1.21(CL 0.65 - 1.78, P < 0.00001) per observation day when fed a lactose-free, high-fiber diet.</p><p><strong>Conclusions: </strong>Lactose-free and high-fiber showed overall the best improvement of the fecal consistency in animals with diarrhea. Switching to commercially available lactose-free diets may decrease diarrhea incidence in rhesus macaques suffering from chronic intermittent idiopathic diarrhea. Nevertheless, additional nutritional research is warranted and establishing optimal nutritional requirements for captive macaques will add to our ability to understand and improve dietary interventions.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ventilator-induced lung injury in rat models: are they all equal in the race?","authors":"Jon Petur Joelsson, Sigurbergur Karason","doi":"10.1186/s42826-025-00240-y","DOIUrl":"10.1186/s42826-025-00240-y","url":null,"abstract":"<p><p>Risk of ventilator-induced lung injury (VILI) is an inevitable and precarious accompaniment of ventilator treatment in critically ill patients worldwide. It can both instigate and aggravate acute respiratory distress syndrome (ARDS) where the only prevention or treatment so far has been empirical approach of what is considered to be lung protective ventilator settings in an attempt to shield the lung tissues against the mechanical stress that unavoidably follows ventilator treatment. The weakened state of the patients limits clinical drug research and pushes for drug discovery in animal models. Mice and rats are often the choice of small animal model, representing about 95% of all laboratory animal studies, as their physiology can mimic that which is found in humans. Mice have been a more popular choice for ventilator studies but due to technical issues, there is some advantage gained in using rats as they are substantially larger. Inducing VILI and ARDS in these models can prove challenging and often the acute nature of the injury used to produce similar tissue damage as in humans does not necessarily fully reflect clinical reality. The aim of this review was to analyse and summarize methods of recent publications in the field, describing what approaches have been utilized to simulate these conditions, possibly identifying a common track enabling comparison of results between studies. However, the study shows a high variety of methods employed by researchers causing comparisons of results difficult and perhaps implying that a more standardized approach should be used.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asian sand dust exacerbates airway inflammation in a mouse model of asthma.","authors":"Se-Jin Lee, So-Won Pak, Woong-Il Kim, Sin-Hyang Park, Young-Kwon Cho, Tae-Won Kim, Je-Won Ko, Joong-Sun Kim, Jong-Choon Kim, In-Hyeon Kim, Sung-Hwan Kim, In-Sik Shin","doi":"10.1186/s42826-025-00243-9","DOIUrl":"https://doi.org/10.1186/s42826-025-00243-9","url":null,"abstract":"<p><strong>Background: </strong>Asian sand dust (ASD), generated from the deserts of China and Mongolia, mainly affects the human health of several countries in Northeast Asia including China, Korea, and Japan. In this study, we investigated the toxic effects of ASD on respiratory tract and explored the effects of ASD exposure on allergic asthma using ovalbumin-induced asthma model. C57BL/6 male mice were used for both the toxicity and allergic asthma studies. ASD (10, 20, and 40 mg/kg) was administered intranasally on days 1, 3, and 5. For allergic asthma, mice were sensitized with OVA (20 µg/mouse) and aluminum hydroxide (2 mg) on days 1 and 15, followed by OVA inhalation (1%, w/v) on days 22, 24, and 26, with subsequent ASD instillation on days 21, 23, and 25.</p><p><strong>Results: </strong>ASD exposure showed the elevation of respiratory inflammation including inflammatory cell infiltration, cytokine production, and mucus secretion with the increase in phosphorylated (p)-nuclear factor-kappa B (NF-κB) p65 expression. In addition, ASD exposure to asthma model significantly increased airway responsiveness, inflammatory cell count and mucus secretion with the elevation of cytokines and immunoglobulin E, which were accompanied with the increases in p-NF-κB p65, p-p38 and cyclooxygenase 2 (COX2).</p><p><strong>Conclusions: </strong>Therefore, ASD exposure induces respiratory inflammation and aggravates the progression of allergic asthma, which was closely associated with the phosphorylation of NF-κB. Respiratory exposure to ASD causes inflammation, upregulation of cytokines, p-NF-κB, and COX2, which can exacerbate asthma.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fludarabine attenuates inflammation and dysregulated autophagy in alveolar macrophages via inhibition of STAT1/IRF1 pathway.","authors":"Jooyeon Lee, Jeong-Ran Park, Hanbyeol Lee, Seok-Ho Hong, Woo Jin Kim, Oliver Eickelberg, Sung-Min Park, Semin Ryu, Sung Joon Cho, Seung-Jin Kim, Se-Ran Yang","doi":"10.1186/s42826-025-00245-7","DOIUrl":"https://doi.org/10.1186/s42826-025-00245-7","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI), including its most severe form, acute respiratory distress syndrome (ARDS), is a common cause of acute hypoxemic respiratory failure. Although its clinical characteristics have been well characterized, the relevant mechanism remains unclear. An imbalance in autophagy leads to alveolar remodeling and triggers the pathogenesis of ARDS. In this study, we assessed the therapeutic efficacy of the STAT1 inhibitor fludarabine (Fluda) in ALI. C57BL6 mice were exposed to lipopolysaccharide (LPS), and their lung tissues were analyzed via next-generation transcriptome sequencing.</p><p><strong>Results: </strong>Western blotting revealed that interferon regulatory factor 1 (IRF1) was highly expressed and STAT1 was phosphorylated following LPS exposure. Fluda significantly decreased the protein expression of STAT1/IRF1 and inhibited the alveolar infiltration of neutrophils and macrophages. Nitric oxide (NO), inducible nitric oxide synthase, tumor necrosis factor-α (TNF-α), interferon-γ, and interleukin-6 (IL-6) release was decreased in the lungs of mice and RAW264.7 macrophages following Fluda treatment. In LPS-induced GFP-LC3 transgenic mice treated with Fluda, the counts of LC3-expressing neutrophils and macrophages in bronchoalveolar (BAL) fluid were significantly decreased. Furthermore, Fluda decreased LC3 and p62 protein expression, thereby inhibiting the release of NO, IL-6, and TNF-α in BAL. In RAW264.7 cells, the inhibition of STAT1/IRF1 by Fluda decreased LPS-induced ERK and NF-κB p65 phosphorylation.</p><p><strong>Conclusions: </strong>The inhibition of STAT1/IRF1 by Fluda plays a pivotal role in modulating dysregulated autophagy by suppressing the MAPK and NF-κB p65 pathways in ALI.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential responses of lung and intestinal microbiota to SARS-CoV-2 infection: a comparative study of the Wuhan and Omicron strains in K18-hACE2 Tg mice.","authors":"Chae Won Kim, Keun Bon Ku, Insu Hwang, Hi Eun Jung, Kyun-Do Kim, Heung Kyu Lee","doi":"10.1186/s42826-025-00241-x","DOIUrl":"https://doi.org/10.1186/s42826-025-00241-x","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic, caused by SARS-CoV-2, has led to the emergence of viral variants with distinct characteristics. Understanding the differential impacts of SARS-CoV-2 variants is crucial for effective public health response and treatment development. We investigated the differential effects of the original Wuhan strain and the emergent Omicron variant of SARS-CoV-2 using a K18-hACE2 transgenic mouse model. We compared the mortality rates, viral loads, and histopathological changes in lung and tracheal tissues, as well as alterations in the lung and intestinal microbiota following infection.</p><p><strong>Results: </strong>Our findings revealed significant differences between the variants, with the Wuhan strain causing higher mortality rates, severe lung pathology, and elevated viral loads compared to the Omicron variant. Microbiome analyses uncovered novel and distinct shifts in the lung and intestinal microbiota associated with each variant, providing evidence for variant-specific microbiome alterations. These changes suggest microbiome-related mechanisms that might modulate disease severity and host responses to SARS-CoV-2 infection.</p><p><strong>Conclusions: </strong>This study highlights critical differences between the Wuhan strain and Omicron variant in terms of mortality, lung pathology, and microbiota changes, emphasizing the role of the microbiome in influencing disease outcomes. Novel findings include the identification of variant-specific microbiota shifts, which underscore potential microbiome-related mechanisms underlying differences in disease severity. These insights pave the way for future research exploring microbiome-targeted interventions to mitigate the impacts of SARS-CoV-2 and other viral infections.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"11"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the protective effects of Spirulina platensis against cyclophosphamide-induced genotoxicity.","authors":"Kouamé Ephrem Zikpi, Aku Enam Motto, Kokou Atchou, Kounouho R Adounkpe Kougblenou, Povi Lawson-Evi, Kwashie Eklu-Gadegbeku","doi":"10.1186/s42826-025-00242-w","DOIUrl":"https://doi.org/10.1186/s42826-025-00242-w","url":null,"abstract":"<p><strong>Background: </strong>Damage to normal cells is the most common limitation of cancer chemotherapy. Cyclophosphamide, one of the most widely used anticancer drugs due to its cytotoxicity, can bind to deoxyribonucleic acid (DNA), causing chromosomal breaks, micronuclei, and cell death. The use of natural sources helps to prevent this damage, and Spirulina platensis is highly appreciated for its numerous bioactive compounds. This study aimed to investigate the antigenotoxic effects of Spirulina platensis powder (PoSP) on mouse bone marrow cells in vivo via a micronucleus assay.</p><p><strong>Results: </strong>Compared to the positive control, the administration of powder significantly reduced the PCE/PCE + NCE (polychromatic erythrocytes, normochromatic erythrocytes) ratio in treated mice. A significant increase in the percentage of MnPCE (micronucleus in polychromatic erythrocytes) in cyclophosphamide-treated bone marrow cells was observed. Compared with the positive controls, the groups treated with different doses in combination with cyclophosphamide presented a significant (p<0.0001) decrease in MnPCE in a dose-dependent manner. Compared to the positive control, PoSP significantly decreased MDA (malondialdehyde) levels in the livers of treated animals. The same things were observed in the kidneys and spleen. The catalase activity was also significantly increased in tissues, compared to negative control.</p><p><strong>Conclusions: </strong>These findings suggest that PoSP does not cause DNA damage and can prevent genotoxicity, probably through its antioxidant activities.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"10"},"PeriodicalIF":2.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring energy expenditure in Göttingen Minipigs using indirect calorimetry: validation and methodological considerations.","authors":"Simon K Bredum, Julie Jacobsen, Susanna Cirera, Berit Ø Christoffersen","doi":"10.1186/s42826-024-00233-3","DOIUrl":"10.1186/s42826-024-00233-3","url":null,"abstract":"<p><strong>Background: </strong>Obesity affects nearly a billion people globally and is associated with various health consequences. Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2-4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate.</p><p><strong>Results: </strong>Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2-4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In sub-study 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted R²: 0.73-0.85).</p><p><strong>Conclusions: </strong>The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"9"},"PeriodicalIF":2.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}