Publications

Latest publication 04/01/2025

Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses

Cellular bioenergetics govern the thermogenic responses to cold stress in thermogenic tissues, and alterations in these processes have the...

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    [title] => Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses
    [paragraph] => Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice
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Authors
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

 Lab

Journal
Journal of Cachexia, Sarcopenia and Muscle
Abstract
Cellular bioenergetics govern the thermogenic responses to cold stress in thermogenic tissues, and alterations in these processes have the potential to affect the overall metabolic status. Thus, we first evaluated the impact of ST or TN housing on molecular processes involved in cellular bioenergetics in SkM. First, as a functional readout of mitochondrial respiratory capacity, we evaluated O2consumption in permeabilized SkM fibres. In C26 mice housed at ST, we observed a tendency for an increased O2consumption in SkM fibres compared to controls (Figure3a). Yet, in mice housed at TN, cancer seemed to lower SkM O2consumption compared to controls. To investigate the outcome of these slight changes in O2consumption, we measured SkM ATP levels. SkM ATP levels were largely unaltered, except for a trend towards a decrease in C26 mice housed at TN (Figure3b). These alterations were independent of changes in mitochondrial mass, measured as TOMM20 protein content (FigureS3a) and mRNA expression of mitochondrial biogenesis markersTfamandPpargc1a(PGC1α) (FigureS3b). Furthermore, protein quantification of different subunits of the OXPHOS complex showed no changes upon cancer or temperature (Figure3c), with the only exception of Complex I (CI), which was 34% lowered by TN. To further understand the housing temperature-dependent effects on ATP levels upon cancer in SkM, we evaluated the activity of the sarco/endoplasmic reticulum Ca2+ATPase (SERCA ATPase), which pumps Ca2+ions from the cytosol to the sarco/endoplasmic reticulum (SR/ER). This requires ATP hydrolysis, and its uncoupling via sarcolipin results in heat dissipation, a key mechanism in nonshivering thermogenesis in SkM [31]. At ST housing, SkM SERCA ATPase activity was increased 4-fold in C26 mice, while at TN, cancer did not influence SkM SERCA ATPase activity (Figure3d). These changes occurred independently of mRNA levels of SR markers SERCA1, SERCA2 and Sarcolipin (Figure3e), and protein levels of SERCA1 and SERCA2 (FigureS3c). Notably, we observed a TN-induced reduction in protein levels of STIM1, an SR/ER-residing Ca2+sensor (FigureS3c). Reduced STIM1 levels have been associated with decreased mitochondria-free Ca2+and respiration [32], which suggests that the underlying molecular systems leading to increased SERCA ATPase activity upon cancer or changes in housing temperature are different.
Keywords/Topics
bioenergetics; cancer cachexia; cold-induced stress; thermogenic tissues; thermoneutrality
BIOSEB Instruments Used:
Grip strength test (BIO-GS4)
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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