Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice
ABSTRACT Background Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temp...
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Wiley
2025-04-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13781 |
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| author | Andrea Irazoki Emma Frank Tang Cam Phung Pham Jessica L. Braun Amy M. Ehrlich Mark Haid Fabien Riols Camilla Hartmann Friis Hansen Anne‐Sofie Rydal Jørgensen Nicoline Resen Andersen Laura Hidalgo‐Corbacho Roberto Meneses‐Valdes Mona Sadek Ali Steffen Henning Raun Johanne Louise Modvig Samantha Gallero Steen Larsen Zach Gerhart‐Hines Thomas Elbenhardt Jensen Maria Rohm Jonas T. Treebak Val Andrew Fajardo Lykke Sylow |
| author_facet | Andrea Irazoki Emma Frank Tang Cam Phung Pham Jessica L. Braun Amy M. Ehrlich Mark Haid Fabien Riols Camilla Hartmann Friis Hansen Anne‐Sofie Rydal Jørgensen Nicoline Resen Andersen Laura Hidalgo‐Corbacho Roberto Meneses‐Valdes Mona Sadek Ali Steffen Henning Raun Johanne Louise Modvig Samantha Gallero Steen Larsen Zach Gerhart‐Hines Thomas Elbenhardt Jensen Maria Rohm Jonas T. Treebak Val Andrew Fajardo Lykke Sylow |
| author_sort | Andrea Irazoki |
| collection | DOAJ |
| description | ABSTRACT Background Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown. Methods Colon 26 carcinoma (C26)‐bearing and PBS‐inoculated (Ctrl) mice were housed at standard (ST; 20°C–22°C) or thermoneutral temperature (TN; 28°C–32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays. Results C26 mice lost 7.5% body weight (p = 0.0001 vs. Ctrls), accounted by decreased fat mass (−35%, p < 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (−40%, p < 0.0001 vs. Ctrls) and increased atrogene expression (3‐fold, p < 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, p < 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (−78%, p < 0.05 vs. ST Ctrl). Thermogenic capacity measured by Ucp1 expression decreased upon cancer in both WAT and BAT (−93% and −63%, p < 0.0044 vs. Ctrls). Cancer‐driven glucose intolerance was noted at ST (26%, p = 0.0192 vs. ST Ctrl), but restored at TN (−23%, p = 0.005 vs. ST C26). Circulating FGF21, GDF‐15 and IL‐6 increased in all C26 mice (4‐fold, p < 0.009 vs. Ctrls), with a greater effect on IL‐6 at TN (76%, p = 0.0018 vs. ST C26). Tumour and WAT Il6 mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) Il6 (2‐fold, p = 0.0016 vs. Ctrls) at both temperatures. BAT Il6 was only induced in C26 mice at TN (116%, p = 0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4‐fold, p = 0.0108 vs. ST Ctrl) but not at TN. In BAT, O2 consumption enhanced in C26 mice at ST (119%, p < 0.03 vs. ST Ctrl) but was blunted at TN (−44%, p < 0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2‐fold, p = 0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (−59%, p = 0.0213 vs. TN Ctrl). Conclusions In mild cachexia, BAT and SkM bioenergetics are susceptible to different housing temperatures, which influences cancer‐induced alterations in glucose metabolism and systemic responses. |
| format | Article |
| id | doaj-art-5cc484a18a17415dbcbb04e4ffbbc879 |
| institution | OA Journals |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-5cc484a18a17415dbcbb04e4ffbbc8792025-08-20T02:35:37ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-04-01162n/an/a10.1002/jcsm.13781Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in MiceAndrea Irazoki0Emma Frank1Tang Cam Phung Pham2Jessica L. Braun3Amy M. Ehrlich4Mark Haid5Fabien Riols6Camilla Hartmann Friis Hansen7Anne‐Sofie Rydal Jørgensen8Nicoline Resen Andersen9Laura Hidalgo‐Corbacho10Roberto Meneses‐Valdes11Mona Sadek Ali12Steffen Henning Raun13Johanne Louise Modvig14Samantha Gallero15Steen Larsen16Zach Gerhart‐Hines17Thomas Elbenhardt Jensen18Maria Rohm19Jonas T. Treebak20Val Andrew Fajardo21Lykke Sylow22Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Kinesiology, Faculty of Applied Health Sciences, Cairns Family Health and Bioscience Research Complex Brock University Niagara Region Ontario CanadaNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkMetabolism & Proteomics Core, Helmholtz Center Munich German Research Center for Environmental Health Neuherberg GermanyMetabolism & Proteomics Core, Helmholtz Center Munich German Research Center for Environmental Health Neuherberg GermanySection of Experimental Animal Models, Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Nutrition, Exercise and Sport University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Nutrition, Exercise and Sport University of Copenhagen Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Nutrition, Exercise and Sport University of Copenhagen Copenhagen DenmarkInstitute for Diabetes and Cancer Helmholtz Center Munich Neuherberg GermanyNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkDepartment of Kinesiology, Faculty of Applied Health Sciences, Cairns Family Health and Bioscience Research Complex Brock University Niagara Region Ontario CanadaDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen DenmarkABSTRACT Background Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown. Methods Colon 26 carcinoma (C26)‐bearing and PBS‐inoculated (Ctrl) mice were housed at standard (ST; 20°C–22°C) or thermoneutral temperature (TN; 28°C–32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays. Results C26 mice lost 7.5% body weight (p = 0.0001 vs. Ctrls), accounted by decreased fat mass (−35%, p < 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (−40%, p < 0.0001 vs. Ctrls) and increased atrogene expression (3‐fold, p < 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, p < 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (−78%, p < 0.05 vs. ST Ctrl). Thermogenic capacity measured by Ucp1 expression decreased upon cancer in both WAT and BAT (−93% and −63%, p < 0.0044 vs. Ctrls). Cancer‐driven glucose intolerance was noted at ST (26%, p = 0.0192 vs. ST Ctrl), but restored at TN (−23%, p = 0.005 vs. ST C26). Circulating FGF21, GDF‐15 and IL‐6 increased in all C26 mice (4‐fold, p < 0.009 vs. Ctrls), with a greater effect on IL‐6 at TN (76%, p = 0.0018 vs. ST C26). Tumour and WAT Il6 mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) Il6 (2‐fold, p = 0.0016 vs. Ctrls) at both temperatures. BAT Il6 was only induced in C26 mice at TN (116%, p = 0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4‐fold, p = 0.0108 vs. ST Ctrl) but not at TN. In BAT, O2 consumption enhanced in C26 mice at ST (119%, p < 0.03 vs. ST Ctrl) but was blunted at TN (−44%, p < 0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2‐fold, p = 0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (−59%, p = 0.0213 vs. TN Ctrl). Conclusions In mild cachexia, BAT and SkM bioenergetics are susceptible to different housing temperatures, which influences cancer‐induced alterations in glucose metabolism and systemic responses.https://doi.org/10.1002/jcsm.13781bioenergeticscancer cachexiacold‐induced stressthermogenic tissuesthermoneutrality |
| spellingShingle | Andrea Irazoki Emma Frank Tang Cam Phung Pham Jessica L. Braun Amy M. Ehrlich Mark Haid Fabien Riols Camilla Hartmann Friis Hansen Anne‐Sofie Rydal Jørgensen Nicoline Resen Andersen Laura Hidalgo‐Corbacho Roberto Meneses‐Valdes Mona Sadek Ali Steffen Henning Raun Johanne Louise Modvig Samantha Gallero Steen Larsen Zach Gerhart‐Hines Thomas Elbenhardt Jensen Maria Rohm Jonas T. Treebak Val Andrew Fajardo Lykke Sylow Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice Journal of Cachexia, Sarcopenia and Muscle bioenergetics cancer cachexia cold‐induced stress thermogenic tissues thermoneutrality |
| title | Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice |
| title_full | Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice |
| title_fullStr | Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice |
| title_full_unstemmed | Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice |
| title_short | Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice |
| title_sort | housing temperature impacts the systemic and tissue specific molecular responses to cancer in mice |
| topic | bioenergetics cancer cachexia cold‐induced stress thermogenic tissues thermoneutrality |
| url | https://doi.org/10.1002/jcsm.13781 |
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