An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and mainly HDL. The decrease in HDL is accompanied by a loss of mainly apoAI-containing particles, an almost total loss of apoCI, and an increase in apoE-containing HDL, as related to the effect of LPS on a wide range of apolipoproteins, plasma enzymes, lipid transfer factors, and receptors that are involved in HDL metabolism. Reciprocally, all lipoprotein classes have been shown to bind LPS and to attenuate the biological response to LPS in vitro and in rodents. Moreover, triglyceride-rich lipoproteins protect rodents against death from LPS and bacterial sepsis. Accumulating evidence indicates that apolipoproteins such as apoE and apoAI, and not the lipid moieties of the particles, may be responsible for these protective effects of lipoproteins. Therefore, to increase our understanding of the complex interaction between lipoprotein metabolism and sepsis, further studies that address the specific roles of apolipoproteins in sepsis are warranted.

Sphingolipids lower plasma cholesterol and triacylglycerol and protect the liver from fat- and cholesterol-induced steatosis.

The role of Kupffer cells (KCs) in the pathophysiology of the liver has been firmly established. Nevertheless, KCs have been underexplored as a target for diagnosis and treatment of liver diseases owing to the lack of noninvasive diagnostic tests. We addressed the hypothesis that cholesteryl ester transfer protein (CETP) is mainly derived from KCs and may predict KC content. Microarray analysis of liver and adipose tissue biopsies, obtained from 93 obese subjects who underwent elective bariatric surgery, showed that expression of CETP is markedly higher in liver than adipose tissue. Hepatic expression of CETP correlated strongly with that of KC markers, and CETP messenger RNA and protein colocalized specifically with KCs in human liver sections. Hepatic KC content as well as hepatic CETP expression correlated strongly with plasma CETP concentration. Mechanistic and intervention studies on the role of KCs in determining the plasma CETP concentration were performed in a transgenic (Tg) mouse model expressing human CETP. Selective elimination of KCs from the liver in CETP Tg mice virtually abolished hepatic CETP expression and largely reduced plasma CETP concentration, consequently improving the lipoprotein profile. Conversely, augmentation of KCs after Bacille-Calemette-Gu erin vaccination largely increased hepatic CETP expression and plasma CETP. Also, lipid-lowering drugs fenofibrate and niacin reduced liver KC content, accompanied by reduced plasma CETP concentration. Conclusions: Plasma CETP is predominantly derived from KCs, and plasma CETP level predicts hepatic