Regulation of hepatic lipase activity by sphingomyelin in plasma lipoproteins

Abstract

Hepatic lipase (HL) is an important enzyme in the clearance of triacylglycerol (TAG) from the circulation, and has been proposed to have pro-atherogenic as well as anti-atherogenic properties. It hydrolyzes both phospholipids and TAG of lipoproteins, and its activity is negatively correlated with HDL levels. Although it is known that HL acts preferentially on HDL lipids, the basis for this specificity is not known, since it does not require any specific apoprotein for activity. In this study, we tested the hypothesis that sphingomyelin (SM), whose concentration is much higher in VLDL and LDL compared to HDL, is an inhibitor of HL, and that this could explain the lipoprotein specificity of the enzyme. The results presented show that the depletion of SM from normal lipoproteins activated the HL roughly in proportion to their SM content. SM depletion stimulated the hydrolysis of both phosphatidylcholine (PC) and TAG, although the PC hydrolysis was stimulated more. In the native lipoproteins, HL showed specificity for PC species containing polyunsaturated fatty acids at sn-2 position, and produced more unsaturated lyso PC species. The enzyme also showed preferential hydrolysis of certain TAG species over others. SM depletion affected the specificity of the enzyme towards PC and TAG species modestly. These results show that SM is a physiological inhibitor of HL activity in lipoproteins and that the specificity of the enzyme towards HDL is at least partly due to its low SM content.

Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice

“…In addition, a significant fraction of dietary LPC-DHA is incorporated directly into intestinal HDL, mainly as phospholipids 17 . It should also be pointed out that the HDL phospholipids are the preferred substrates for three different enzymes in the plasma, namely lecithin-cholesterol acyltransferase 34 , hepatic lipase 35 , and endothelial lipase 36 , all of which are known to generate LPC-DHA, the preferred carrier of DHA into brain 13 – 15 .…”

Effect of dietary DHA/EPA ratio on the early development, antioxidant response and lipid metabolism in larvae of Siberia sturgeon (Acipenser baerii, Brandt)

“…The transcription factor PPARs play key roles in the catabolism and storage of fatty acids (Kjӕr, Todorčević, Torstensen, Vegusdal, & Ruyter, ; Viswakarma et al, ), in which PPARα is a vital gene that could increase fatty acid oxidation in adipocytes, and its expression levels could reflect the presence of β‐oxidation (Dong et al, ; Zheng et al, ; Zuo, Ai, Mai, & Xu, ). Together with LPL, HL is responsible for the clearance of TG from the circulation (Yang & Subbaiah, ). HL encodes hepatic triglyceride lipase mainly expressed in liver and has the dual functions of TG hydrolase and ligand factor for receptor‐mediated lipoprotein uptake, especially for HDL‐C metabolism (Annema & Tietge, ; Zambon et al, ).…”

Hepatocyte-specific, PPARγ-regulated mechanisms to promote steatosis in adult mice

“…Mass spectra were acquired and recorded by Analyst software (AB Sciex, version 6.1). The major neutral lipids species known to be present in the liver tissues were analyzed in MRM mode, with the transition from its ammoniated ion (Q1) to the product ion derived from the loss of its ammoniated fatty acid (Q3) (Yang and Subbaiah 2015). Quantification of individual molecular species was performed from the relative intensities of the various species and the corresponding internal standards respectively.…”