**9. References**

208 Dyslipidemia - From Prevention to Treatment

apoB gene was unaffected after 16 h of LPS challenge in the treated animals. It cannot be discarded that transcriptional activation may occur transiently during other stages of the

Another aspect involved in regulating mRNA level is the modulation of mRNA stability through regulatory elements residing in the 3'- and 5'-untranslated region (UTR) and adequate RNA binding proteins. HuR is an important protein in stabilizing inflammatory AU-rich elements (ARE)-bearing RNAs. Human apoB mRNA has been reported to contain ARE sequences at 3'-UTRs and bioinformatic analysis of rat apoB transcript revealed the presence of AU-rich regions. Our results demonstrated the specific binding of stabilizing HuR protein to the rat apoB mRNA, although there were no superior binding in livers from LPS treated rats. Consequently, in our conditions it is not likely that apoB mRNA half-life was extended by HuR binding, but we can not discard a role for other stabilizing proteins or

changes in the mRNA degradation pathway, but further analysis is need (Fig 5).

Fig. 5. Endotoxin induce increase in apoB mRNA without altering transcription rate or HuR

During the septic response, altered VLDL metabolism is responsible for the lipemia of sepsis. Entotoxin promoted changes are biphasic. In the early stage hypertriglyceridemia is accompanied by increased circulating fatty acids levels and a rise in large TG-rich VLDL, whereas the later stage is characterized by high levels of hepatic apoB transcript and TG-

APR.

protein binding.

**7. Conclusion** 


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**11** 

*Spain* 

**Peroxisome Proliferator-Activated Receptor** 

**β/δ (PPAR β/δ) as a Potential Therapeutic** 

*Spanish Biomedical Research Centre in Diabetes and Associated Metabolic* 

Dyslipidemia is a powerful predictor of cardiovascular disease in patients at high risk (Turner et al., 1998), such as type 2 diabetic patients. Lowering of LDL-C is the prime target for treatment (2002), but even with intensification of statin therapy, a substantial residual cardiovascular risk remains (Barter et al., 2007; Miller et al., 2008; Fruchart et al., 2008; Shepherd et al., 2006). This may partly be due to atherogenic dyslipidemia. This term is commonly used to describe a condition of abnormally elevated plasma triglycerides and low high-density lipoprotein cholesterol (HDL-C), irrespective of the levels of LDL-C (Grundy, 1995). In addition to these key components, increased levels of small, dense LDL-C particles are also present, which in conjunction with the former components conform the also called "lipid triad" (Shepherd et al., 2005). Other abnormalities include accumulation in plasma of triglyceride-rich lipoproteins (TLRs), including chylomicron and very-low-density lipoprotein (VLDL) remnants. This is reflected by elevated plasma concentrations of non-HDL-C and apolipoprotein B-100 (apoB). Postprandially, there is also accumulation in plasma of TLRs and their remnants, as well as qualitative alterations in LDL and HDL particles. Thus, hypertriglyceridemia is associated with a wide spectrum of atherogenic lipoproteins not measured routinely (Taskinen, 2003). The presence of this lipid plasma profile with high triglyceride and low HDL-C levels have been shown to increase the risk of cardiovascular events independent of conventional risk factors (Bansal et al., 2007; Barter et al., 2007; deGoma et al., 2008). In fact, guidelines recommend modifying high triglyceride and low HDL-C as secondary therapeutic targets to provide additional vascular protection (2002). The presence of atherogenic dyslipidemia is seen in almost all patients with triglycerides > 2.2 mmol/l and HDL-C < 1.0 mmol/l, virtually all of whom have type 2 diabetes or abdominal obesity and insulin resistance (Taskinen, 2003). Most of these alterations are also characteristic of metabolic syndrome, which is defined as the clustering

**1. Introduction** 

Emma Barroso, Lucía Serrano-Marco, Laia Salvadó,

*Disorders(CIBERDEM)-Instituto de SaludCarlos III and IBUB,* 

Xavier Palomer and Manuel Vázquez-Carrera *Department of Pharmacology and Therapeutic Chemistry,* 

*(Biomedicine Institute of the University of Barcelona), Faculty of Pharmacy, University of Barcelona, Barcelona,* 

**Target for Dyslipidemia** 

Zu, L., He, J., Jiang, H., Xu, C., Pu, S., & Xu, G. (2009). Bacterial endotoxin stimulates adipose lipolysis via toll-like receptor 4 and extracellular signal-regulated kinase pathway. *J Biol. Chem.*, Vol.284, No.9, pp. 5915-5926, ISSN 0021-9285
