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**10** 

*Spain* 

**Disrupted VLDL Features and** 

**Lipoprotein Metabolism in Sepsis** 

Patricia Aspichueta, Nerea Bartolomé, Xabier Buqué, María José Martínez, Begoña Ochoa and Yolanda Chico

*Department of Physiology, Faculty of Medicine, University of the Basque Country* 

Gram-negative sepsis is an increasingly clinical syndrome triggered by exposure to bacterial lipopolysaccharide (LPS) or endotoxin. It is associated with a plethora of physiological and biochemical changes, known as acute-phase response (APR), including disturbances in serum lipid and lipoprotein levels (Khovidhunkit et al., 2004). Within the blood, LPS is extracted by the acute phase reactant LPS-binding protein (LBP) and transferred to CD14 receptor on monocytes and macrophages. The CD14 associates with Toll like receptor 4, myeloid differentiation-2 and other proteins forming a receptor cluster that leads to LPSinduced activation (Triantafilou & Triantafilou, 2005), resulting in the release of soluble

Kupffer cells (KC), the resident machrophages in the liver, secrete cytokines, particularly tumor necrosis factor α (TNF-α) and the interleukins (IL) IL-6 and IL-1β, that act as paracrine factors on neighboring hepatocytes and promote many of the metabolic changes that accompany the acute-phase response. One of the most striking changes associated to sepsis is the accumulation of triglycerides (TG) within very low density lipoprotein (VLDL) in the plasma, partly ascribed to an increased hepatic VLDL production and a decreased peripheral metabolism driven by pro-inflammatory cytokines. These metabolic alterations, clinically termed as the "lipemia of sepsis", have been postulated to be components of the

In this chapter we summarize the actual knowledge on sepsis induced alterations in VLDL metabolism, lipids and apoB availability and the involvement of inflammatory mediators.

Elevation of plasma lipid levels is an early hallmark of sepsis, clinically defined as lipemia of sepsis. The rise in circulating lipids is mainly caused by a rapid accumulation of triglycerides within very low density lipoproteins (Esteve et al., 2005; Khovidhunkit et al., 2004), although other lipids such as non-esterified fatty acids coming from peripheral tissue lipolysis (Khovidhunkit et al., 2004), or cholesterol, in the case of rodents, can also be elevated (Feingold et al., 1993). However, decreases in cholesterol associated to high density lipoproteins (HDL) have been reported as a characteristic associated to sepsis in primates

**1. Introduction** 

mediators, such as proinflammatory cytokines.

**2. Hiperlipemia of sepsis** 

and rodents (Khovidhunkit et al., 2004).

innate defensive reaction against infection (Harris et al., 2000).

