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Volume 26
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10.3390/ijms26167898
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice

by
Elena Elsukova
1,
Tatiana Zamay
2,3,
Anna Kichkailo
2,3,
Andrey Yakunenkov
1,
Dmitry V. Veprintsev
2,
Zoran Minic
4,
Maxim V. Berezovski
4 and
Yury Glazyrin
2,3,*
1
Department of Biology, Chemistry and Teaching Methods, Krasnoyarsk State Pedagogical University named after V.P. Astafyev, Ady Lebedevoy 82, 660049 Krasnoyarsk, Russia
2
Laboratory for Digital Controlled Drugs and Theranostics, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, Akademgorodok 50, 660036 Krasnoyarsk, Russia
3
Laboratory for Biomolecular and Medical Technologies, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Partizana Zheleznyaka 1, 660022 Krasnoyarsk, Russia
4
Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Core Facility, University of Ottawa, Ottawa, ON K1N 6N5, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(16), 7898; https://doi.org/10.3390/ijms26167898
Submission received: 14 July 2025 / Revised: 6 August 2025 / Accepted: 14 August 2025 / Published: 15 August 2025
(This article belongs to the Special Issue Molecular Associations Between Adipose Tissue and Diseases)
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Abstract

Adipose tissue exhibits dynamic metabolic and structural changes in response to environmental stimuli, including temperature fluctuations. While continuous cold exposure has been extensively studied, the molecular effects of prolonged intermittent cold exposure (ICE) remain poorly characterized. Here, we present a proteomic analysis of inguinal white adipose tissue (IWAT) from mice subjected to a 16-week regimen of short-term daily ICE (6 °C for 6 h, 5 days per week) without compensatory caloric intake. Mass spectrometry identified 1108 proteins, with 140 differentially expressed between experimental and control groups. ICE significantly upregulated mitochondrial proteins associated with lipid and carbohydrate catabolism, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipogenesis, including LETM1, AIFM1, PHB, PHB2, ACOT2, NDUA9, and ATP5J. These changes reflect enhanced metabolic activity and mitochondrial remodeling. In contrast, proteins linked to oxidative stress, insulin resistance, inflammation, and extracellular matrix remodeling were downregulated, such as HMGB1, FETUA, SERPH1, RPN1, and AOC3. Notably, gamma-synuclein (SYUG), which inhibits lipolysis, was undetectable in ICE-treated samples. Our findings support the hypothesis that ICE promotes thermogenic reprogramming and metabolic rejuvenation in subcutaneous fat through activation of futile cycles and mitochondrial restructuring. This study offers molecular insights into adaptive thermogenesis and presents intermittent cold exposure as a potential strategy to mitigate adipose tissue aging.
Keywords: proteomics; adipose tissue; intermittent cold exposure; mitochondrial remodeling; thermogenesis; futile cycles proteomics; adipose tissue; intermittent cold exposure; mitochondrial remodeling; thermogenesis; futile cycles
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MDPI and ACS Style

Elsukova, E.; Zamay, T.; Kichkailo, A.; Yakunenkov, A.; Veprintsev, D.V.; Minic, Z.; Berezovski, M.V.; Glazyrin, Y. Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice. Int. J. Mol. Sci. 2025, 26, 7898. https://doi.org/10.3390/ijms26167898

AMA Style

Elsukova E, Zamay T, Kichkailo A, Yakunenkov A, Veprintsev DV, Minic Z, Berezovski MV, Glazyrin Y. Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice. International Journal of Molecular Sciences. 2025; 26(16):7898. https://doi.org/10.3390/ijms26167898

Chicago/Turabian Style

Elsukova, Elena, Tatiana Zamay, Anna Kichkailo, Andrey Yakunenkov, Dmitry V. Veprintsev, Zoran Minic, Maxim V. Berezovski, and Yury Glazyrin. 2025. "Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice" International Journal of Molecular Sciences 26, no. 16: 7898. https://doi.org/10.3390/ijms26167898

APA Style

Elsukova, E., Zamay, T., Kichkailo, A., Yakunenkov, A., Veprintsev, D. V., Minic, Z., Berezovski, M. V., & Glazyrin, Y. (2025). Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice. International Journal of Molecular Sciences, 26(16), 7898. https://doi.org/10.3390/ijms26167898

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