Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice

Abstract

Combined lipase deficiency ( cld ) is a recessive mutation in mice that causes a severe lack of lipoprotein lipase (LPL) and hepatic lipase (HL) activities, hyperlipemia, and death within 3 days after birth. Earlier studies showed that inactive LPL and HL were synthesized by cld / cld tissues and that LPL synthesized by cld / cld brown adipocytes was retained in their ER. We report here a study of HL in liver, adrenal, and plasma of normal newborn and cld / cld mice. Immunofluorescence studies showed HL was present in extracellular space, but not in cells, in liver and adrenal of both normal and cld / cld mice. When protein secretion was blocked with monensin, HL was retained intracellularly in liver cell cultures and in incubated adrenal tissues of both groups of mice. These findings demonstrated that HL was synthesized and secreted by liver and adrenal cells in normal newborn and cld / cld mice. HL activities in liver, adrenal, and plasma in cld / cld mice were very low, Ͻ 8% of that in normal newborn mice, indicating that HL synthesized and secreted by cld / cld cells was inactive. Livers of both normal newborn and cld / cld mice synthesized LPL, but the level of LPL activity in cld / cld liver was very low, Ͻ 9% of that in normal liver. Immunofluorescence studies showed that LPL was present intracellularly in liver of cld/cld mice, indicating that LPL was synthesized but not secreted by cld/ cld liver cells. Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL. Livers of both groups of mice contained an unidentified alkaline lipase activity which accounted for 34-54% of alkaline lipase activity in normal and 65% of that in cld / cld livers. Our findings indicate that liver and adrenal cells synthesized and secreted HL in both normal newborn and cld / cld mice, but the lipase was inactive in cld/cld mice. That cld / cld liver cells secreted inactive HL while retaining inactive LPL indicates that these closely related lipases were processed differently. -Schultz, C. J., E. J. Blanchette-Mackie, and R. O. Scow. Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld / cld mice.

Identification of mouse and human macrophages as a site of synthesis of hepatic lipase

“…While expression of the HL gene in macrophages is a novel finding, expression of this gene in tissues other than liver has been previously reported. HL in mouse adrenals has been demonstrated by immunohistochemistry (29) and HL has been found in rat ovaries and adrenals (2,3). Both adrenals and ovaries from rat synthesize a variant mRNA that lacks exons 1 and 2 (4,5).…”

Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion

“…hLPL is retained in the ER of cld cells and appears to be misfolded, suggesting that a factor required for correct folding of hLPL is defective or absent in cld cells (15). Studies by Shultz, Blanchette-Mackie, and Scow (17) suggest that at least a portion of mHL is secreted from cld liver and adrenals, but is presumably either inactive or rapidly cleared from the circu-lation, as no HL activity is detected in the plasma of cld animals (17). Results in the present study also demonstrate secretion of mHL from cld cells, and, moreover, suggest that the secreted enzyme is active.…”

“…However, immunofluorescence data from Schultz, Blanchette-Mackie, and Scow (17) demonstrate secretion of HL by liver and adrenals of cld mice. The secreted HL is presumably either inactive or rapidly cleared from the circulation, as no significant HL activity was detected in the plasma of these animals (17). The question of whether HL mass is present in the plasma of cld mice has not been addressed, presumably because of the lack of anti-mouse HL (mHL) antibodies.…”