Obesity-driven musculotendinous remodeling impairs tissue resilience to mechanical damage

Cesanelli, L, Minderis, P, Balnyte, I, Ratkevicius, A, Degens, H ORCID: https://orcid.org/0000-0001-7399-4841 and Satkunskiene, D (2025) Obesity-driven musculotendinous remodeling impairs tissue resilience to mechanical damage. Cell and Tissue Research. ISSN 0302-766X

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Abstract

Obesity has been associated with lower muscle strength-to-body mass ratio. Here, we evaluated the effects of diet-induced obesity on the mechano-structural properties of isolated muscles and tendons. Thirty 10-week-old male C57BL/6 J mice were randomly assigned to either an obesogenic high-fat diet group (OB) for 24 weeks or a control group (CN) maintained on a standard chow diet. Soleus muscle (SOL) and Achilles tendon (AT) specimens were isolated and subjected either to failure testing, 300 cycles of passive stretch-destretch, or isometric twitch contractions. Morpho-structural and protein expression analyses were conducted to assess collagen and adipose tissue accumulation, concentrations of cross-linking factors, and any alterations in the POSTN-TGFβ1-Akt signaling pathway. OB SOL and AT tissues were more fragile than those from CN (p < 0.05). A piecewise linear regression model revealed a tendency for OB tissues to exhibit steeper mechanical property changes within the first 20 cycles compared to CN, followed by a similar plateau phase in both groups. OB SOL-AT complexes showed a slower twitch-contraction-relaxation pattern than CN (p < 0.05). OB tendons and muscles were larger than those of the CN, with muscles featuring bigger fibers, and higher collagen area fraction (p < 0.05). Elevated TGFβ1 and POSTN concentrations were observed in OB tissues (p < 0.05), alongside increased P-Akt and P-4EBP1 expression (p < 0.05). These findings highlight the detrimental effects of obesity on the structural integrity of muscle and tendon tissues and suggest a significant role of POSTN-TGFβ1-Akt signaling in obesity-associated musculotendinous remodeling.