Glycerolipid intermediates as signaling mediators in physiology and disease

Abstract

Lipids have a number of essential biological roles that, despite a wealth of knowledge, somehow remain understudied. Glycerolipids are a major form of stored energy, play important structural functions as hydrophobic components of cell membranes, and have dynamic effects on signaling mediators within the cell and to distant tissues. Generally, it was believed that the pathways that synthesized lipids for these functions were distinct, compartmentalized, and did not widely intersect. For example, the main pathways for triglyceride storage as an energy source were not thought to play major roles in regulating the synthesis of lipids for signaling cascades even though many intermediates play roles as activators of intracellular kinases. However, it is now better appreciated that some of these storage intermediates also have signaling functions. In most cells, a pathway utilizing glycerol‐3‐phosphate as its initial substrate is the major route of triglyceride synthesis. Glycerol‐3‐phosphate undergoes two sequential acylations and then is dephosphorylated by lipin proteins to form diacylglycerol. Modulating the activity of lipin 1, a phosphatidic acid phosphohydrolase, has profound effects on skeletal muscle, adipose tissue, cardiac, and hepatic signaling by regulating the cellular abundance of phosphatidic acid. Evidence will be presented that lipin 1‐mediated signaling effects regulate metabolic flux, mitochondrial homeostasis, autophagy, cardiac and skeletal myocyte function, and impact cell death processes. These studies demonstrate that lipin 1 mediated effects on the concentrations of these intermediates are not important for storing energy, but also impact critical signaling cascades that control cellular homeostasis.Support or Funding InformationSupported by NIH grants R01 HL119225 and R01 DK78187This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.