Biosynthesis of the vasoactive lipid monobutyrin. Central role of diacylglycerol.

Monobutyrin (1-butyrylglycerol) is a simple lipid secreted by adipocytes that stimulates both angiogenesis and vasodilation of microvascular beds. While monobutyrin production is increased during lipolysis, little is known about the biosynthetic pathway of this short chain monoacylglycerol. We show here that diacylglycerol, an intermediate in the lipolytic pathway, can stimulate monobutyrin synthesis from an adipocyte particulate fraction and does so by acting as a substrate. The biosynthetic route involves the acylation of diacylglycerol with butyryl-CoA to form a transient triacylglycerol intermediate. This intermediate is then hydrolyzed by a lipase(s) with specificity for long chain fatty acyl groups to form monobutyrin. Based on this information, a novel pathway for the synthesis of monobutyrin is proposed. Preliminary characterization of these enzymatic activities with respect to their cell-type specificity indicates that the acyltransferase activity is found in several cell types, albeit at lower levels than in adipocytes. The lipase activity appears to be two distinct steps, with both steps being adipocyte differentiation-dependent. These results indicate the likely biochemical basis for the restriction of monobutyrin synthesis to fat cells and also suggests a molecular basis for the close linkage between lipolysis, monobutyrin synthesis, and vasodilation.