Data availability
The data generated in this study, including uncropped blot scans, are provided in the Source Data files. Source data are provided with this paper. No custom code was used in this study. Source data are provided with this paper.
References
Silva, J. E. Thermogenic mechanisms and their hormonal regulation. Physiol. Rev. 86, 435–464 (2006).
Sentis, S. C., Oelkrug, R. & Mittag, J. Thyroid hormones in the regulation of brown adipose tissue thermogenesis. Endocr. Connect 10, R106–R115 (2021).
Tsibulnikov, S., Maslov, L., Voronkov, N. & Oeltgen, P. Thyroid hormones and the mechanisms of adaptation to cold. Horm.-Int. J. Endocrino. 19, 329–339 (2020).
Rosen, E. D. & Spiegelman, B. M. What we talk about when we talk about fat. Cell 156, 20–44 (2014).
Kajimura, S., Spiegelman, B. M. & Seale, P. Brown and beige fat: physiological roles beyond heat generation. Cell Metab. 22, 546–559 (2015).
Chouchani, E. T., Kazak, L. & Spiegelman, B. M. New advances in adaptive thermogenesis: UCP1 and Beyond. Cell Metab. 29, 27–37 (2019).
Evans, S. S., Repasky, E. A. & Fisher, D. T. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat. Rev. Immunol. 15, 335–349 (2015).
Chouchani, E. T. & Kajimura, S. Metabolic adaptation and maladaptation in adipose tissue. Nat. Metab. 1, 189–200 (2019).
Riley, N. et al. Dietary lipids are largely deposited in skin and rapidly affect insulating properties. Nat. Commun. 16, 4570 (2025).
Speakman, J. R. Obesity and thermoregulation. Handb. Clin. Neurol. 156, 431–443 (2018).
Zhang, Z. et al. Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice. J. Clin. Invest. 129, 5327–5342 (2019).
Kasza, I. et al. Syndecan-1 is required to maintain intradermal fat and prevent cold stress. PLoS Genet. 10, e1004514 (2014).
Zamboni, M. et al. Adipose tissue, diet and aging. Mech. Ageing Dev. 136-137, 129–137 (2014).
Gordon, L. B., Rothman, F. G., López-Otín, C. & Misteli, T. Progeria: a paradigm for translational medicine. Cell 156, 400–407 (2014).
Lopez-Mejia, I. C. et al. Antagonistic functions of LMNA isoforms in energy expenditure and lifespan. EMBO Rep. 15, 529–539 (2014).
Sun, S. et al. Vascular endothelium-targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model. Sci. Adv. 6, eaay5556 (2020).
Osorio, F. G. et al. Splicing-directed therapy in a new mouse model of human accelerated aging. Sci. Transl. Med. 3, ra107 (2011).
Hamczyk, M. R. et al. Vascular smooth muscle-specific progerin expression accelerates atherosclerosis and death in a mouse model of Hutchinson-Gilford progeria syndrome. Circulation 138, 266–282 (2018).
Costa, D. G., Ferreira-Marques, M. & Cavadas, C. Lipodystrophy as a target to delay premature aging. Trends Endocrinol. Metab. 35, 97–106 (2024).
Kang, S. M., Yoon, M. H. & Park, B. J. Laminopathies; mutations on single gene and various human genetic diseases. BMB Rep. 51, 327–337 (2018).
Lee, K. Y. et al. Lessons on conditional gene targeting in mouse adipose tissue. Diabetes 62, 864–874 (2013).
Imai, T. et al. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse. Proc. Natl. Acad. Sci. USA 101, 4543–4547 (2004).
Cannon, B. & Nedergaard, J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J. Exp. Biol. 214, 242–253 (2011).
Tan, C. L. et al. Warm-sensitive neurons that control body temperature. Cell 167, 47 (2016).
Warner, A. et al. Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor alpha1. Proc. Natl. Acad. Sci. USA 110, 16241–16246 (2013).
Hotamisligil, G. S. Inflammation, metaflammation and immunometabolic disorders. Nature 542, 177–185 (2017).
Kreienkamp, R. et al. A cell-intrinsic interferon-like response links replication stress to cellular aging caused by progerin. Cell Rep. 22, 2006–2015 (2018).
Tan, C. L. & Knight, Z. A. Regulation of body temperature by the nervous system. Neuron 98, 31–48 (2018).
Patrignani, P. & Patrono, C. Cyclooxygenase inhibitors: from pharmacology to clinical read-outs. Biochim. Biophys. Acta 1851, 422–432 (2015).
Pajvani, U. B. et al. Fat apoptosis through targeted activation of caspase 8: a new mouse model of inducible and reversible lipoatrophy. Nat. Med. 11, 797–803 (2005).
Yamauchi, T. et al. Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. Nat. Genet. 30, 221–226 (2002).
Palmer, B. F. & Clegg, D. J. The sexual dimorphism of obesity. Mol. Cell Endocrinol. 402, 113–119 (2015).
Pan, R. & Chen, Y. Fat biology and metabolic balance: on the significance of sex. Mol. Cell Endocrinol. 533, 111336 (2021).
Kurylowicz, A. Estrogens in adipose tissue physiology and obesity-related dysfunction. Biomedicines 11, 690 (2023).
Fischer, A. W., Csikasz, R. I., von Essen, G., Cannon, B. & Nedergaard, J. No insulating effect of obesity. Am. J. Physiol.-Endoc. M. 311, E202–E213 (2016).
Cannon, B. & Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359 (2004).
Kim, J. et al. Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice. Aging 8, 2392–2406 (2016).
Conti, B. et al. Transgenic mice with a reduced core body temperature have an increased life span. Science 314, 825–828 (2006).
Zhao, Z. J. et al. Body temperature is a more important modulator of lifespan than metabolic rate in two small mammals. Nat. Metab. 4, 320 (2022).
Mehlem, A., Hagberg, C. E., Muhl, L., Eriksson, U. & Falkevall, A. Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease. Nat. Protoc. 8, 1149–1154 (2013).
Qu, Q. et al. Lithocholic acid phenocopies anti-ageing effects of calorie restriction. Nature 643, 192–200 (2025).
Yue, H. et al. A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue. J. Pharm. Biomed. Anal. 43, 1122–1134 (2007).
Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (grant nos. 32430048, 82125012, and 82488301 to B.L., 32090033, 82071578, and 82360282 to Z.L.), the Shenzhen Medical Research Fund (C2406001), the National Key R&D Program of China (2024YFA0918700, 2023YFC2509900, 2021ZD0202400 to B.L.), the Guangdong Basic and Applied Research Foundation (2025A1515010719 to W.S.), the Shenzhen Science and Technology Talent Project (RCYX2023121109012703 to W.S.), the Shenzhen Municipal Commission of Science and Technology Innovation (JCYJ20220818100016035 and JCYJ20220818100009020 to B.L.), the Shenzhen University 2035 Program of Excellent Research (0000214 to W.S.), and the Shenzhen University Medicine Plus Program (2024YG017 to W.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors are grateful to Dr. Jessica Tamanini (Shenzhen University and ETediting) for editing the manuscript prior to submission.
Author information
Author notes
These authors contributed equally: Zuojun Liu, Wenjing Hu, Xiaoqing Tan, Shimin Sun.
Authors and Affiliations
Shenzhen Key Laboratory for Systemic Aging and Intervention (SKL-SAI), Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Marshall Laboratory of Biomedical Engineering, International Cancer Center, National Health Commission Key Laboratory of Bone Aging, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China
Zuojun Liu, Wenjing Hu, Xiaoqing Tan, Shimin Sun, Minxian Qian, Xiaolong Tang & Baohua Liu
Department of Environmental Health, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan University, Haikou, 570228, China
Zuojun Liu
Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255000, China
Wenjing Hu, Weiwei Wu & Qiuxiang Pang
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University, Jena, Germany
Wenjing Hu & Shimin Sun
Shenzhen Key Laboratory of Anti-Aging and Regenerative Medicine, Department of Pathology and Pathophysiology School of Basic Medical Sciences, Shenzhen University, Shenzhen, 518055, China
Xin Huang, Nan Zhao, Zimei Wang & Wen Su
School of Basic Medical Sciences, Wannan Medical University, Wuhu, 241002, China
Yuan Meng & Ming Wang
Authors
- Zuojun Liu
- Wenjing Hu
- Xiaoqing Tan
- Shimin Sun
- Xin Huang
- Yuan Meng
- Nan Zhao
- Ming Wang
- Weiwei Wu
- Minxian Qian
- Xiaolong Tang
- Qiuxiang Pang
- Zimei Wang
- Wen Su
- Baohua Liu
Contributions
B.L., Z.L., and W.S. conceived the project and designed the experiments. W.H., X.T., and S.S. performed most of the experiments. X.H., Y.M., and N.Z. helped in the animal experiments. M.W., W.W., M.Q., X.Tang, Q.P., and Z.W. provided technical support and discussed some results. Z.L., W.S., and B.L. wrote the manuscript.
Corresponding authors
Correspondence to Wen Su or Baohua Liu.
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. [A peer review file is available].
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Source data
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Liu, Z., Hu, W., Tan, X. et al. White adipose atrophy exacerbates cold stress and accelerates aging in male mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71857-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-026-71857-3

