Intramuscular fat links to spinal muscle loss and weakness
People with intramuscular fat fractions above 10% showed significantly lower paraspinal muscle mass and strength than those with levels below 5%.
Advanced Science
In people with spinal sarcopenia, researchers found that the intramuscular fat fraction, rather than perimuscular fat fraction, was an independent determinant of trunk muscle strength. Single-nucleus RNA sequencing of fat-infiltrated human paraspinal muscle revealed remodeling of muscle architecture, extracellular matrix organization, and satellite cell niches.
The profiling identified a GPC3-positive fibro/adipogenic progenitor subpopulation with enhanced lipogenic potential, marked by high expression of GPC3, PPARG, ADIPOQ, and FABP4. Among adipose-derived factors, ANGPTL4 emerged as a paracrine suppressor of myogenesis, acting through the upregulation of syndecan-2 in satellite cells. In cultured mouse C2C12 cells, inhibiting syndecan-2 partially rescued the myogenic impairment caused by ANGPTL4 exposure.
Why it matters
Fat infiltration into skeletal muscle is a major contributor to age-related frailty and functional decline. Identifying cellular transitions and paracrine signals in the muscle niche offers candidate pathways for preserving muscle quality in sarcopenia.
Caveats
The patient findings rely on observational, cross-sectional data that link fat fraction to muscle loss without establishing causality. Additionally, functional rescue of the ANGPTL4-syndecan-2 axis was evaluated in cultured mouse C2C12 cells rather than in human muscle tissue.
- Resources: datasets, atlases and tools
- Extracellular matrix
- ANGPTL4
- Sarcopenia
- Intramuscular fat fraction
- Humans
The paper
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Quanzhong Ren, Ling Wang, Fangfang Duan, Guihe Yang, Ruixuan Yu, Yi Wang, Yingyu Zhang, Zetong Zang, Chuqi Li, Weijia Liu, Wenshuang Zhang, Yi Yuan, Zitong Cheng, Xiaoguang Cheng, Junbo Liang,Beijing Jishuitan Hospital
Advanced Science · 4 Oct 2026
