Ghrelin attenuates skeletal-muscle atrophy by regulating muscle protein degradation and lung inflammation in aged male mice with lipopolysaccharide-induced lung injury.
Level 5 - mechanism / opinion, no new human data
Preclinical animal (aged mice) and in vitro (C2C12 myotubes) laboratory study.
PubMed 41722618 · doi:10.1016/j.peptides.2026.171478
What was done
Aged male mice with lipopolysaccharide (LPS)-induced lung injury were treated with intraperitoneal ghrelin administered every 12 hours. Investigators evaluated gastrocnemius muscle mass, contractile force, voluntary wheel-running activity, FoxO1-dependent E3 ubiquitin ligases (muscle RING-finger protein-1 and F-Box protein 32), histological lung damage, and inflammatory cytokine concentrations in bronchoalveolar lavage fluid. In vitro experiments in LPS-stimulated C2C12 myotubes examined reactive oxygen species accumulation, muscle-specific ubiquitin ligase expression, and redox-regulatory genes (PGC-1α and SOD2).
What was found
The abstract reports qualitative directions of effect without reporting numerical values, effect sizes, or confidence intervals. In aged mice with LPS-induced lung injury, ghrelin preserved muscle weight and mass, suppressed FoxO1-dependent MuRF-1 and Fbxo32 expression, and improved muscle contractile force and voluntary wheel-running activity. Ghrelin also decreased histological lung injury and lowered bronchoalveolar lavage fluid inflammatory cytokines. In vitro, ghrelin suppressed LPS-induced ROS accumulation and ubiquitin ligase expression, and increased expression of PGC-1α and SOD2.
Why it matters
This paper identifies mechanisms by which ghrelin signaling reduces acute pulmonary inflammation and concurrent muscle catabolism in an aged animal model. It provides preclinical rationale for investigating ghrelin receptor agonists for secondary respiratory sarcopenia.
Limits
The study is entirely preclinical (in vitro cell culture and aged male mice), limiting direct translation to clinical human sarcopenia. The abstract does not report sample sizes, drug dosages, or quantitative numerical data with variance. Only male mice were tested, preventing evaluation of sex-specific differences.
Cited by
- supports Lipopolysaccharide (LPS) administration causes extensive muscle wasting and sarcopenia over time in experimental models.