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Cross-bridge Cycle

Cross-bridge Cycle

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Adipose-Muscle Crosstalk in COPD Cachexia: Early Adipose Atrophy Drives Subsequent Muscle Wasting.

Takashi Shimada¹, Shotaro Chubachi¹, Keisuke Nishikawa¹

¹Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Journal of Cachexia, Sarcopenia and Muscle

|December 9, 2025

Summary

In chronic obstructive pulmonary disease (COPD) cachexia, adipose tissue atrophy occurs before muscle wasting. Adipose tissue dysfunction contributes to muscle atrophy, suggesting it as a therapeutic target.

Keywords:

adipose tissue atrophy cachexia chronic obstructive pulmonary disease muscle wasting

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Area of Science:

Pulmonary Medicine
Metabolic Disorders
Cellular Biology

Background:

Chronic obstructive pulmonary disease (COPD) is linked to cachexia, impacting prognosis and quality of life.
Mechanisms of adipose tissue atrophy, its role, and interaction with skeletal muscle in COPD cachexia are poorly understood.
Hypothesis: Adipose tissue atrophy precedes muscle wasting in COPD cachexia, with adipose-muscle crosstalk driving progression.

Purpose of the Study:

To investigate the temporal relationship between adipose tissue and skeletal muscle atrophy in COPD.
To elucidate the underlying pathophysiological mechanisms of cachexia in COPD.
To explore the role of adipose-muscle crosstalk in COPD cachexia.

Main Methods:

Analysis of CT scans from 185 COPD patients to quantify muscle and adipose tissue areas and emphysema.
Histological and molecular analyses in a cigarette smoke-induced emphysema mouse model.
In vitro studies using adipocytes and myotubes exposed to cigarette smoke extract (CSE).

Main Results:

COPD patients showed negative correlations between muscle/adipose tissue areas and emphysema severity.
In mice, adipose tissue atrophy and inflammation preceded muscle atrophy.
In vitro, CSE induced adipose dysfunction and atrophy, which in turn promoted myotube atrophy.

Conclusions:

Cigarette smoke-induced adipose tissue atrophy precedes muscle wasting in COPD.
Adipose tissue dysfunction plays a role in the progression of muscle atrophy in COPD cachexia.
Adipose tissue represents a potential therapeutic target for COPD-associated cachexia.