出版社:American Society for Biochemistry and Molecular Biology
摘要:Apolipoprotein B (apoB)-dependent and apoB-independent pathwaysfor cholesterol transport have been described in cultured cells.Here, we show that the apoB-independent pathway involves apoA-I-containinghigh density lipoproteins (HDLs). Cholesterol secretion by theHDLs, but not by the apoB pathway, was significantly reducedin primary enterocytes isolated from chow- and cholesterol-fedapoA-I–/– mice. These enterocytes were capable ofcholesterol efflux when apoA-I was provided extracellularly.In apoA-I–/– mice, the absorption of a bolus ofcholesterol was similar in control and apoA-I–/–mice fed chow or high-cholesterol diet. However, short-termstudies revealed that cholesterol absorption was occurring overlonger lengths of the intestine, and cholesterol but not triglyceridetransport to the plasma and liver in chow- and cholesterol-fedapoA-I–/– mice was significantly reduced.
These studies indicate that in apoA-I deficiency, there is adelay in cholesterol absorption, but cholesterol is eventuallyabsorbed because of the compensatory apoB pathway. Nonetheless,long-term studies involving multiple feedings showed significantreduction in cholesterol absorption after 4 days. We proposethat multiple compensatory mechanisms ensure efficient cholesterolabsorption in mice.Abbreviations: ABCA1, ATP binding cassette protein A1; apoB, apolipoprotein B; HDL, high density lipoprotein; OA, oleic acid; TC, taurocholate