Acid and Neutral Lipases of Cultured Adipocytes of Infants and Children

Abstract

SummaryIn order to determine whether the mobilization of intracellular triglycerides observed in cultured human adipocytes is associated with changes in the activities of acid and neutral lipases, the activities of both enzymes were measured weekly on cultured adipocytes for several months. The activity of acid lipase was initially very low, but rose to levels 40 times the original activity within 3 months. The activity of neutral lipase decreased rapidly within the first 2-4 weeks and remained at approximately 25% of original levels thereafter. SpeculationThere is increasing evidence that the human adipocyte is highly specialized and that it is derived from a stromal precursor present in the adipose tissue. The cell has the capacity to acquire in culture the properties of the precursor, as evidenced by the appearance of acid lipase and disappearance of neutral lipase. We submit that the low level of acid lipase in the adipocyte is related to its lipid storage function. It remains to be proven that it is not primary to the differentiation of the adipocyte from its ~uhhermore, we speculate that a direct biochemical relations hi^ exists between the neutral lipase and intracellular triglyceride Aores in the adipocyte.Although lipid mobilization from adipose tissue appears to be under the control of a number of endogenous and exogenous influences, the final step in mobilization is hydrolysis of triglycerides by lipases. Neutral lipases have been characterized in the adipose and other tissues of a number of species (4-7, 11-17, 20, 21, 23, 27, 29-33). They are active at neutral pH, have affinity for long chain triglyceride esters, and sensitive to hormones such as epinephrine and insulin. Acid lipases are lysosoma1 in subcellular location (13,20,32). First described in the liver (13,28,32), acid lipases are active around pH 4.0 and appear to have a somewhat broader chain length preference. In adipose tissue, an acid lipase, which could be stimulated by lipolytic hormones (18, 28) has been described as sedimenting with mitochondria (18,28). This is the class of lipases deficient in the tissues of patients with lipidoses such as Wolman's disease and cholesteryl ester storage disease (8).Earlier, we showed that human adipose cells can be sustained in culture for long periods of time (1, 2) and have described some of the morphologic and enzymatic properties of these cells in culture (2). Other investigators (9, 24, 34) have also established presumptive "preadipose" or adipose cells in culture. In one study (24), cultured "preadipose cells" accumulated triglycerides and incorporated glucose into lipids, thus resembling adipose cells rather than skin fibroblasts. In a recent study, Van et al. (34) found measurable levels of lipoprotein lipase activity in cultured "adipocyte precursors" of human adipose tissue. These putative "preadipose cells" were also found to possess 15 times as much triglyceride synthetase activity as skin fibroblast from the same patients and twice the fatty acid synthetase activity. Dixon-Shanies ...