In a study published in SCIENCE CHINA Life Sciences on February 21, Prof. YIN Yulong from the Institute of Subtropical Agriculture, Chinese Academy of Sciences uncovered compelling evidence linking LPS-induced muscle mass loss to the reduction of Bacteroidetes abundance, increased inflammation, and disruption of mitochondrial morphology.

Using a chronic immune stress piglet model induced by lipopolysaccharide (LPS), the researches conducted in-depth and series of experiments to explore the growth and developmental dynamics of intestinal, liver, and muscle tissues in weaned piglets under immune stress.

Through extensive analysis, the researchers determined that inflammation is key in the pathogenesis of skeletal muscle atrophy. Chronic inflammation is marked by an imbalance of pro- and anti-inflammatory macrophages, leading to a protein degradation and compromised muscle growth. This study highlights that chronic immune stress resulted in a decrease in muscle mass and body weight, which persisted even after 15 days. This observation contrasts with the initial liver and intestinal damage that showed recovery in later phases. The main period during which muscle damage occurred was the early stage of stress (1~5 day).

More interestingly, when researchers analyzed the changes in the gut microbiota following LPS injection, a significant decrease were observed in the relative abundance of Bacteroidetes, accompanied by increased levels of pro-inflammatory cytokines.

The researchers then validated that mitochondrial dysfunction and morphological impairments were identified as pivotal factors in muscle mass loss. Early mitochondrial changes preceded muscle weight loss in piglets, with significant alterations in key mitochondrial dynamics proteins like Drp1 and OPA1.

"These insights mark a significant advancement in our understanding of muscle growth impairment in livestock and human health.” said Prof DUAN Yehui, corresponding auther of the stuy. “Our data may provide potential therapeutic targets to prevent muscle mass loss.”

This work was supported by the National Natural Science Foundation of China, the science and technology innovation Program of Hunan Province, the Changsha Natural Science Funds for Distinguished Young Scholar, and the National Key Research and Development Programs of China.

Contact: Duan Yehui

E-mail: duanyehui@isa.ac.cn

Molecular mechanisms of chronic immune stress-induced muscle growth inhibiton in piglet model (Image by Yu Jiayi)