Hepatitis C virus (HCV) exerts a profound influence on host lipid metabolism. It has been suggested that the synthesis of both fatty acids (FA) and cholesterol is dysregulated in HCV but this has not been directly quantified in humans. The purpose of this study was to measure lipogenesis and cholesterol synthesis using stable isotopes in patients with HCV (n = 5) and healthy control (n = 9) subjects recruited from the University of Alberta hospital. Blood samples were taken at fasting (0 and 24 hours) and after meals over the day to mimic typical food consumption and postprandial metabolism. Isolation of free cholesterol (FC), cholesteryl ester (CE), and triglyceride (TG) from plasma and very low-density lipoproteins (VLDL) was used to measure FA and cholesterol synthesis using deuterium uptake and isotope ratio mass spectrometry. FA composition was analyzed by gas chromatography. VLDL-TG levels of polyunsaturated fatty acids (PUFA), including linoleic and linolenic acid, were lower in HCV compared to control ( P < 0.05 for both). Fasting hepatic lipogenesis was significantly higher in HCV (2.80 ± 0.55%) compared to control (1.19 ± 0.27%; P = 0.03). Conversely, fasting whole-body synthesis of FC (HCV 1.64 ± 0.28% versus control 8.78 ± 1.59%) and CE (HCV 0.26 ± 0.08% versus control 1.92 ± 0.25%), as well as hepatic FC synthesis (HCV 1.68 ± 0.26% versus control 8.12 ± 0.77%) was lower in HCV ( P < 0.001 for all). Conclusion : These data provide evidence that lipogenesis is elevated while cholesterol synthesis is impaired in HCV, supporting previous findings from cellular and animal models. Low PUFA levels combined with elevated lipogenesis suggests a role for dietary PUFA supplementation in HCV patients.

Gangliosides are integral to the structure and function of cell membranes. Ganglioside composition of the intestinal brush border and apical surface of the colon influences numerous cell processes including microbial attachment, cell division, differentiation, and signaling. Accelerated catabolism of ganglioside in intestinal disease results in increased proinflammatory signaling. Restoring proper structure and function to the diseased intestine can resolve inflammation, increase resistance to infection, and improve gut integrity to induce remission of conditions like necrotizing enterocolitis (NEC) and Crohn's disease (CD). Maintaining inactive state of disease may be achieved by reducing the rate that gangliosides are degraded or by increasing intake of dietary ganglioside. Collectively, the studies outlined in this paper indicate that the amount of gangliosides GM3 and GD3 in intestinal mucosa is decreased with inflammation, low level of GM3 is associated with higher production of proinflammatory signals, and ganglioside content of intestinal mucosa can be increased by dietary ganglioside.

Objective: To investigate policosanol absorption by brush border membrane (BBM), metabolism in CaCo-2 enterocytes, and transport of policosanol metabolites across the basolateral membrane (BLM). It was hypothesized that policosanol is partially oxidized into fatty acids and then is incorporated into other lipids. Methods: Policosanol was emulsified with phosphatidylcholine in the culture medium. The viability of cells was assessed via an MTT (3-[4,5]dimethylthiazol-2-yl-2,5-diphenyltetrazolim) assay. Control cells received only the same amount of “vehicle” (phosphatidylcholine) without policosanol. CaCo-2 cell monolayer and medium were collected; lipid was extracted and analyzed by thin-layer chromatography (TLC) and gas liquid chromatography (GLC). Results: Eighty-six percent of policosanol added to the cell culture medium was absorbed after 48 hours' incubation. The amount of cholesterol ester fatty acid was significantly increased both in the cells and in the basolateral medium, and was reduced in the apical medium. Policosanol increased the quantity of free fatty acids in the basolateral medium and reduced the free fatty acid content of CaCo-2 cells. Further evaluation of lipid profiles indicated that policosanol modulated the fatty acid profile of cholesterol ester in the basolateral medium. Conclusion: It was concluded that policosanol or policosanol metabolites may modulate lipid metabolism and/or transport following absorption by the BBM, partial oxidation by the intestinal epithelium, and transport of policosanol metabolites across the BLM.