1640-P: Meroterpenoid-Rich Ethanolic Extract of Sargassum serratifolium (MES) Alters Macrophage Transcriptome and Secretion Profile toward Improving Muscle Atrophy and Glucose Intolerance

Abstract

Skeletal muscle plays an essential role in glucose homeostasis. Of many cell types in the skeletal muscle, recent studies indicate that secretion factors derived from macrophages are important for glucose metabolism in the skeletal muscle. Here, RNA Sequencing analysis showed that Lipopolysaccharide (LPS) treatment broadly altered the transcriptome of macrophages, of which signaling related to secretion factors was markedly altered toward elevating unfavorable cytokines to maintain skeletal muscle metabolism. On the other hand, the treatment of the Meroterpenoid-Rich Extract of Sargassum Serratifolium (MES), a strong anti-inflammatory and antioxidant extract found in our previous studies, reversed the LPS-induced signaling pathways. We further tested whether the treatment of conditioned media (CM) derived from LPS-macrophage (LPS-CM) or CM derived from LPS-macrophage treated with MES (MES-CM) affects glucose homeostasis in differentiated C2C12 myotube cells. LPS-CM treatment notably increased mRNA levels of muscle atrophy-associated genes including MuRF1, MAFbx, and Myostatin, and decreased glucose uptake, and MES-CM treatment reversed these characteristics, indicating that secretion factors induced by LPS or MES either impair or improve muscle glucose homeostasis, respectively. We further analyzed secretion factors inside by proteome array and data showed that LPS-CM includes GDF-15, IL-1 α/β, RAGE, etc related to muscle atrophy and glucose intolerance, which were significantly reduced in MES-CM. These data indicate that LPS- or MES-induced changes in the transcriptome in macrophages are closely related to the alteration in secretion factors toward either impairing or improving glucose metabolism in the skeletal muscle respectively. Of many, the decrease in macrophage-derived cytokine mentioned above may be important for glucose homeostasis in the skeletal muscle. Disclosure H.Ryu: None. B.Lee: None.