Biliary Acid Concentration Research Articles

Palmitic Acid Induced a Dedifferentiation Profile at the Transcriptome Level: A Collagen Synthesis but no Triglyceride Accumulation in Hepatocyte-Like Cells Derived From Human-Induced Pluripotent Stem Cells Cultivated Inside Organ on a Chip.

Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of critical liver diseases leading to steatosis, steatohepatitis, fibrosis, and ultimately to liver cirrhosis and hepatic carcinoma. In this study, the effect of palmitic acid (PA), one of the most abundant dietary fatty acids, was investigated using an organ-on-a-chip (OoC) technology on hepatocyte-like cells derived from human-induced pluripotent stem cells (hiPSCs). After 1 week of hepatic maturation, followed by 1 week of exposure, the transcriptomic analysis showed lower liver transcription factor activity. It also revealed that 318 genes were differentially expressed between the control and 0.5-mM PA conditions. The 0.5-mM PA conditions were characterized by the downregulation of hepatic markers (liver transcription factors, phase I and phase II metabolism genes) of lipidic genes (metabolism and transport). In parallel, the 0.5-mM PA treatment upregulated several extracellular matrix genes (such as collagen genes). The physiopathological staining demonstrated no lipid accumulation in our model and confirmed the secretion of collagen in the 0.5-mM PA conditions. However, the production of albumin, the metabolic biotransformation by the cytochrome P450 enzymes, and the biliary acid concentrations were not altered by the PA treatments. Overall, our data illustrated the response to PA characterized by an early stage of dedifferentiation observed at the transcriptomic levels associated with a modification of the collagenic profile but without lipid accumulation. We believe that our model provides new insight of the onset of palmitic lipotoxicity in the early stage of NAFLD.

Goat Milk Feeding Causes an Increase in Biliary Secretion of Cholesterol and a Decrease in Plasma Cholesterol Levels in Rats

The hypocholesterolemic effect of goat milk with respect to cow milk observed in a previous study led us to examine the influence of goat and cow milk in the diet on certain aspects of biliary physiology in normal rats. The fat content in all diets was 10% but the lipid quality was varied: the standard diet was based on virgin olive oil, and the other 2 diets included fat obtained from lyophilized cow milk and goat milk. We characterized the bile secretion, including biliary phospholipid, cholesterol, and bile acid outputs, the interrelation between bile acids and bile lipids, and the lithogenic index. The consumption of goat milk in the diet, compared with that of cow milk, caused an increase in the biliary secretion of cholesterol together with a decrease in plasma cholesterol concentration, whereas values for bile phospholipids, biliary acid concentrations, and the lithogenic index remained normal. Moreover, consumption of this type of milk decreased plasma triglyceride concentration and therefore had a positive effect, similar to that of olive oil (standard diet), on the lipid metabolism; hence, it may be recommended for consumption by the general population.

Influence de la forme d’apport des lipides de la graine de lin sur le métabolisme du cholestérol chez le hamster

Dietary intake of whole linseeds exerts a beneficial effect on lipid metabolism and risk factors of cardiovascular diseases, due in particular to the abundance of a-linolenic acid (ALA). The effect of the form of ALA providing, either as whole extruded seeds, or as linseed oil combined with linseed meal was investigated on parameters of lipid metabolism in the male hamster, and compared to that of a diet of same gross composition, but rich in saturated fatty acids (SFA). Replacing SFA by ALA (as oil or seeds) decreased significantly plasma cholesterol concentration (-28%), the effect being more pronounced on LDL (-49%) than on HDL (-17%). There was no difference between the two forms of ALA providing on cholesterol intestinal absorption (82-85%) and plasma transport. By contrast, providing ALA as whole seeds resulted in a lesser hepatic cholesterol accumulation (-24%), and in a greater biliary acid concentration in bile (+ 20%), possibly indicative of a better cholesterol elimination. The synergy between the effect of fibres and that of ALA on hepatobiliary metabolism of cholesterol would therefore be enhanced when both components are provided as whole linseed, rather than separately.