Correlation of molecular and cellular signatures in primary skeletal muscle satellite cells derived from lean and diet-induced obese mice

TL;DR

This study found that short-term high-fat diets in mice do not alter the behavior or molecular signatures of skeletal muscle stem cells in laboratory conditions.

Contribution

The study shows that primary satellite cell cultures are not affected by 8 weeks of high-fat diet in vitro, suggesting they are better for acute metabolic testing.

Findings

No differences in proliferation or differentiation of myoblasts from lean and diet-induced obese mice.

Molecular markers for myogenesis, senescence, autophagy, and oxidative stress remained unchanged in vitro.

Short-term high-fat diet effects on satellite cells may not be detectable in primary cultures.

Abstract

Obesity resulting from chronic overnutrition and physical inactivity promotes the development of metabolic disorders by disrupting physiological processes in metabolically active organs, including skeletal muscles. To investigate whether skeletal muscle stem cells (satellite cells, SCs) are affected by systemic metabolic stress, we established primary SC cultures from male mice fed a high-fat diet (HFD) for 8 wk, and from control mice fed a standard chow (CTL). This model allowed us to assess diet-induced obesity (DIO)–related changes in SC-specific molecular and cellular signatures. Although body weight, body fat composition, and adipose tissue-associated macrophages differed significantly between DIO and CTL ex vivo, we observed no differences in the in vitro behaviour of primary SC-derived myoblasts from either group. Parameters such as proliferation and differentiation following serum deprivation were comparable. Expression levels and distribution patterns of myogenic regulatory factors (MRF), SC-specific markers (Pax7, CD56, Itga7), and hallmarks for senescence (GLB1), autophagy (p62, LC3B), and oxidative stress (ALDH1A1, ALDH1A3) remained unchanged. Thus, potential differences in the signatures of SC-derived myoblasts after 8 wk of a high-fat diet cannot be depicted in vitro. However, future experiments should address whether prolonged and metabolically more susceptible diets will exert long-term effects on myogenesis in vitro or not. Overall, we propose that primary SC cultures are better suited for acute in vitro testing regarding the molecular and cellular plasticity in metabolic shifts as induced by pharmacological treatments or genetical modifications, rather than for modeling long-term dietary effects.

The online version contains supplementary material available at 10.1007/s11626-025-01130-2.

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