Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice
Muscular atrophy is among the systematic decline in organ functions in aging, while defective thermogenic fat functionality precedes these anomalies. The potential crosstalk between adipose tissue and muscle during aging is poorly understood. In this study, it is showed that UCP1 knockout (KO) mice characterized deteriorated brown adipose tissue (BAT) function in aging, yet their glucose homeostasis is sustained and energy expenditure is increased, possibly compensated by improved inguinal adipose tissue (iWAT) and muscle functionality compared to age-matched WT mice. To understand the potential crosstalk, RNA-seq and metabolomic analysis were performed on adipose tissue and muscle in aging mice and revealed that creatine levels are increased both in iWAT and muscle of UCP1 KO mice. Interestingly, molecular analysis and metabolite tracing revealed that creatine biosynthesis is increased in iWAT while creatine uptake is increased in muscle in UCP1 KO mice, suggesting creatine transportation from iWAT to muscle. Importantly, creatine analog β-GPA abolished the differences in muscle functions between aging WT and UCP1 KO mice, while UCP1 inhibitor α-CD improved muscle glycolytic function and glucose metabolism in aging mice. Overall, these results suggested that iWAT and skeletal muscle compensate for declined BAT function during aging via creatine metabolism to sustain metabolic homeostasis.
Authors
- Shuang Yu (ORCID: https://orcid.org/0000-0002-5604-0293)
- Wenhao Zhou (ORCID: https://orcid.org/0000-0001-8956-7238)
- Cen Xie (ORCID: https://orcid.org/0000-0002-4574-8456)
- Sainan Xu
- Lingyan Xu (ORCID: https://orcid.org/0000-0002-8666-5219)
- Mingwei Guo (ORCID: https://orcid.org/0000-0001-8081-6912)
- Xinran Ma (ORCID: https://orcid.org/0000-0003-4968-6536)
- Jin Qiu
- Yiwen Wang (ORCID: https://orcid.org/0000-0003-2495-6552)
- Jian Yu (ORCID: https://orcid.org/0000-0001-8449-8739)
- Ziqi Liu (ORCID: https://orcid.org/0009-0005-3566-5824)
- Zixuan Li (ORCID: https://orcid.org/0009-0004-3831-5144)
- Yutang Cao
- Juntong Chen (ORCID: https://orcid.org/0000-0001-9343-4032)
- Xiaozhen Guo (ORCID: https://orcid.org/0000-0001-6852-6015)
- Sainan Wang (ORCID: https://orcid.org/0000-0002-8510-185X)
- Yuhan Guo (ORCID: https://orcid.org/0009-0002-7088-4940)
- Dongmei Wang (ORCID: https://orcid.org/0000-0002-9230-7530)
- Jun Zhang (ORCID: https://orcid.org/0000-0002-3067-2620)
- Jiaqi Li (ORCID: https://orcid.org/0000-0003-4211-9299)
Institutions
- Chongqing Normal University (CN)
- Nanjing University of Chinese Medicine (CN)
- Chinese Academy of Sciences (CN)
- Xian Central Hospital (CN)
- Shanghai Institute of Materia Medica (CN)
- University of Chinese Academy of Sciences (CN)
- Southern Medical University (CN)
- East China Normal University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-11-21
- DOI
- https://doi.org/10.1002/advs.202411015
- Citations
- 11
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 3.59
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- China Postdoctoral Science Foundation
- Science and Technology Commission of Shanghai Municipality
- East China Normal University
- Natural Science Foundation of Chongqing
- Centre Scientifique et Technique du Bâtiment
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities