Lipid Mapping of Lipid Signaling Mediators in Skeletal Muscle
Authors: Daniel Merina , Brotto Leticia , Huang Jian , Awad Kamal , Brotto Marco 
Published: May 2024

Recent advancements in lipidomic have provided profound insight that goes beyond considering lipids as simple organic compounds that constitute the fundamental components of cell membranes. Beyond their pivotal roles in processes such as energy storage and serving as the fundamental building blocks of life, lipids have emerged as potent signaling molecules of significance. The importance of lipid signaling stems from its ability to orchestrate cellular responses to many environmental stresses, including salinity and pathogen attacks. Lipid signaling plays a significant role by allowing cells to respond to their local environment through reactions such as cell differentiation, inflammation and even immunity. In context with this knowledge, our objective is to comprehensively identify key signaling lipid mediators documented from published scientific literature, followed by a systemic visualization of the resulting data through the process of lipid mediator mapping to identify common signaling mediators pathways/networks that are essential for musculoskeletal (MSK) health and disease. These bioinformatics studies are complemented by our experimental studies in muscle cells. To this end, we are using a customized liquid chromatography-mass spectrometry (LC-MS) approach to profile and quantify lipid mediators (LMs). We were able to identify and profile up to 214 LMs and to precisely quantify 60 of them from various samples including body fluid, plasma, serum, bone marrow, muscle tissue, and other cell tissues. Preliminary screening indicated that 11,12-EET, 12-HETE, and PGE2 are three LMs that regulate physiologic aspects in muscles. In addition, 11,12-EET contributes to the regulation of vasodilation, exhibits anti-inflammatory properties under some conditions and in some specific tissues, and maintains endothelial function, and vascular health. However, our data indicates that 11, 12-EET levels increase with aging, decrease with exercise, and is causal for osteopenia in a zebrafish model, supporting our hypothesis that the effects of LMs are tissue specific and related to environmental factors. PGE2, which also causes inflammation, seems to be a putative LM implicated in tissue regeneration in multiple organs. In skeletal muscles, we found that PGE2 enhances myogenic differentiation and proliferation of muscle cells up to nM concentration. PGE2 also possesses beneficial bronchoprotective and anti-inflammatory effects on the airways. In conclusion, this combination of bioinformatics and experimental studies to deepen the mapping of signaling pathways and networks of LMs is crucially needed to understand the full function of LMs in MSK health and disease. This work was directly supported by NIH-National Institutes of Aging P01AG039355 (MB) and the George W. and Hazel M. Jay and Evanston Research Endowments (MB). Authors were supported by NIH Grants: National Institutes of Aging (NINDS) 2-R01NS105621; NIA-R01AG056504, NIA-2R01AG060341, National Institutes of Diabetes, Digestive, and Kidney Diseases Kidney (NIDDK)-1R01DK119066 to MB, and National Institutes of Neurological Disorders and Stroke (NINDS) 2-R01NS105621 to MB. Also, NIH/NIDC 1R01DE031872-01 (VV). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.