Modulation of murine hepatic lipase activity by exogenous and endogenous Kupffer-cell activation

Abstract

Deficiency of hepatic lipase (HL) may play a role in the lipoprotein abnormalities in chronic inflammatory states which are characterized by reticuloendothelial-system activation and cytokine release. HL triacylglycerol hydrolase activity was measured in heparin perfusates of livers from autoimmune MRL/lpr mice, which spontaneously develop a condition closely resembling human lupus erythematosis and exhibit spontaneous Kupffer-cell activation after 8 weeks of age, as well as from normal mice treated with Corynebacterium parvum or polyinosinic-polycytidylic acid complex [poly(I.C)] to induce Kupffer-cell activation. HL activity in MRL/lpr mice older than 8 weeks was 29.5% (P = 0.002) of that in age-matched control MRL/++ mice. Treatment of normal mice with C. parvum or poly(I.C) resulted in HL activities 18.6% (P = 0.004) and 13.1% (P = 0.007) respectively of untreated controls. Northern-blot hybridization of liver poly(A)+ RNA showed no differences in HL mRNA abundance in MRL/++ mice compared with the MRL/lpr autoimmune strain after 8 weeks of age, or in normal control mice compared with those treated with C. parvum, indicating attenuation of HL activity at the translational or post-translational level. Deficiency of this enzyme may represent one of the mechanisms contributing to the dyslipoproteinaemia of autoimmune disease and chronic infection.

Endotoxin and cytokines decrease serum levels and extra hepatic protein and mRNA levels of cholesteryl ester transfer protein in syrian hamsters.

“…The activity of hepatic lipase is decreased by endotoxin and inflammation (7)(8)(9)(10). Hepatic lipase is responsible for metabolizing large triglyceride-rich HDL into smaller HDL 2 , which is more rapidly cleared from the circulation, and to pre ␤ 1 HDL, which is believed to play a key role in mediating the transfer of free cholesterol from cell membranes (11)(12)(13).…”

LIGHT/TNFSR14 Can Regulate Hepatic Lipase Expression by Hepatocytes Independent of T Cells and Kupffer Cells

“…HL is synthesized primarily in the liver by hepatocytes and is regulated as a function of cholesterol homeostasis and several physiological and pharmacological factors [9] and by inflammatory factors such as IL-1β [30], autoimmunity [38] and the acute phase response [39], [40]. T cell activation is a hallmark of inflammatory responses and LIGHT is expressed on T cells during activation.…”