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LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose Intolerance

  • Heeyeon Ryu (Department of Food Science and Nutrition, Pukyong National University) ;
  • Hyeon Hak Jeong (Department of Smart Green Technology Engineering, Pukyong National University) ;
  • Seungjun Lee (Department of Food Science and Nutrition, Pukyong National University) ;
  • Min-Kyeong Lee (Department of Food Science and Nutrition, Pukyong National University) ;
  • Myeong-Jin Kim (Department of Food Science and Nutrition, Pukyong National University) ;
  • Bonggi Lee (Department of Food Science and Nutrition, Pukyong National University)
  • 투고 : 2023.09.28
  • 심사 : 2023.11.22
  • 발행 : 2024.02.28

초록

Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

키워드

과제정보

This work was supported by the Korea Institute of Marine Science & Technology Promotion (20220252) and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (821030-3). This work was also supported by the National Research Foundation of Korea (RS-2023-00274576).

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