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- Title
Biphasic adaptative responses in VLDL metabolism and lipoprotein homeostasis during Gram-negative endotoxemia.
- Authors
Bartolomé, Nerea; Aspichueta, Patricia; Martínez, María J; Vázquez-Chantada, Mercedes; Martínez-Chantar, María L; Ochoa, Begoña; Chico, Yolanda
- Abstract
Dyslipidemia and hepatic overproduction of very low density lipoprotein (VLDL) are hallmarks of the septic response, yet the underlying mechanisms are not fully defined. We evaluated the lipoprotein subclasses profile and hepatic VLDL assembly machinery over 24 h in fasted LPS-treated rats. The response of serum non-esterified fatty acids (NEFA) and glucose to endotoxin was biphasic, with increased levels of NEFA and hypoglycemia in the first 12 h-phase, and low NEFA and high glucose in the second 12 h-phase. Hypertriglyceridemia was more marked in the first 12 h (6.8-fold), when triglyceride abundance increased in all lipoprotein subclasses, and preferentially in large VLDL. The abundance of medium-sized VLDL and the increase in the number of VLDL particles was higher in the second phase (10-fold vs 5-fold in the first phase); however, apoB gene transcript abundance increased only in the second phase. Analysis of putative pre-translational mechanisms revealed that neither increased Apob transcription rate nor increased transcript binding to mRNA stabilizing HuR (Hu antigen R) protein paralleled the increase in apoB transcripts. In conclusion, endotoxin challenge induces increases in plasma NEFA and large, triglyceride-rich VLDL. After approximately 12 h, the triglyceride-rich VLDLs are replaced by medium-sized, triglyceride-poor VLDL particles. Hepatic apoB mRNA abundance also increases during the second period, suggesting a role for apoB protein expression in the acute reaction against sepsis.
- Subjects
LOW density lipoproteins; LIPOPROTEINS; GRAM-negative bacteria; ENDOTOXEMIA; APOLIPOPROTEIN B; METABOLISM; DYSLIPIDEMIA; GENE expression
- Publication
Innate Immunity, 2012, Vol 18, Issue 1, p89
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425910390722