Introduction:
Dyslipidemia is one of the major risk factors of atherosclerosis and coronary heart diseases (CHD). Therapeutic elevation of HDL and particularly its functionality helps to prevent the development of CHD. The anti-atherogenic effect of HDL has been attributed to its main functional and structural protein, Apolipoprotein A-I, which can be produced by the small intestines and the liver. Recently, propionate (C3) supplementation was found to reduce atherosclerosis in experimental models. This is in line with earlier observations suggesting a protective role for SCFA in CHD development. Our studies try to find a role for SCFA on HDL metabolism and as such provide further experimental evidence for the importance of short chain fatty acids (SCFA) in promoting host cardiovascular health.

Methods & Results:
Human liver cells (HepG2) were cultured with and without SCFAs (propionic acid C3, butyric acid C4, valeric acid C5 and hexanoic acid C6) in the presence or absence of a cytokine cocktail (TNF-α and IL-1β) for 48 hours. Cells were harvested to determine ApoA-I expression by real-time qPCR. To investigate the effects of SCFA on NF-kβ transcriptional activity, we transfected hepatic cells with NF-kβ luciferase reporter gene. To investigate the effects of SCFA on pro-inflammatory cytokine expression, we measured IL-8 secretion in HepG2 cells medium using ELISA. SCFA elevates ApoA-I mRNA expression dose-dependently and blunts the inflammation-induced reduction in ApoA-I mRNA expression. Furthermore, SCFA blunts the cytokine-induced NF-kb transactivation. Moreover, SCFA dose-dependently lowers IL-8 protein secretion.


Conclusion:
SCFA stimulate ApoA-I mRNA expression in HepG2 cells in normal and inflammatory conditions. Moreover, SCFA decrease NF-kB transactivation, which may contribute to the anti-inflammatory effects reflected in a decreased IL-8 secretion.

06 - SHORT CHAIN FATTY ACIDS MODULATE THE TRANSCRIPTION AND SECRETION OF APOLIPOPROTEIN A-I IN HUMAN HEPATOCYTES IN VITRO