# Disuse‐induced muscle‐type specific alterations and adiponectin pathway response in male mice

## TL;DR

This study shows how disuse causes muscle atrophy and affects the adiponectin pathway differently in two types of mouse muscles.

## Contribution

The study reveals muscle-type specific responses to disuse in adiponectin signaling and myofiber changes.

## Key findings

- HLUI causes more severe atrophy in the Tibialis anterior than in the Soleus muscle.
- HLUI increases hybrid myofibers and alters adiponectin levels and forms in a muscle-type dependent manner.
- Adiporeceptors are downregulated in the Soleus but not in the Tibialis anterior after disuse.

## Abstract

Disuse‐mediated Muscle Atrophy (DMA) causes persistent muscle weakness, limiting exercise training as a treatment. Adiponectin (ApN) emerged as a therapeutic candidate for muscle disorders. However, the effect of DMA on the ApN pathway remains poorly studied. Given ApN's metabolic effects, examining the ApN pathway response to disuse in relation with muscle type is essential. To mimic DMA while avoiding confounding factors, we combined HindLimb Unloading with Immobilization (HLUI) through a device allowing mouse displacements. The effects of disuse on DMA severity were studied in the slow‐twitch Soleus and the fast‐twitch Tibialis anterior (TA) muscles, together with the ApN pathway. The Soleus muscle presents a moderate atrophy of type IIa myofibers, whereas the TA muscle is more severely affected and exhibits a type I to IIa switch. HLUI increased the hybrid I/IIa myofiber proportion in both muscles, suggesting an ongoing myofiber switch that is delayed in the Soleus muscle. Concomitantly, HLUI enhances ApN plasma level, modifies oligomeric form proportions, and downregulates Adiporeceptors in the Soleus but not in the TA muscle. In conclusion, HLUI is associated with a higher ApN plasma level and disturbances in oligomeric form proportions. DMA severity, myofiber switch kinetics, and adiporeceptor regulation are muscle‐type dependent.

(LeftPanel) HindLimb Unloading combined with Immobilization (HLUI) was used to induce Disuse Muscle Atrophy (DMA) via an optimized device that allow mouse displacements along the cage. As a result of muscle positioning during immobilization, the Soleus muscle was stretched and the Tibialis anterior (TA) muscle was shortened. (Right Panel) Fiber‐type‐specific effects of HLUI were studied in both muscles, along with the ApN pathway. TheSoleus shows moderate type IIa atrophy (↓CSA, in green); TA displays a more severe atrophy in type IIa (↓CSA, in green) and IIb (↓CSA, in orange) fibers, as well as a type I to IIa shift (↓I, in red). Hybrid I/IIa fibers increase in both muscles (↑I/IIa). HLUI elevates ApN plasma level (↑ApN), alters ApN oligomeric forms (↓LMW, ↑MMW), and downregulates adiporeceptors in the Soleus (↓AdipoR1, ↓AdipoR2), but not in the Tibialis anterior (TA) muscle.