TY - JOUR
T1 - Relative roles of ABCG5/ABCG8 in liver and intestine
AU - Wang, Jin
AU - Mitsche, Matthew A.
AU - Lütjohann, Dieter
AU - Cohen, Jonathan C.
AU - Xie, Xiao Song
AU - Hobbs, Helen H.
N1 - Publisher Copyright:
© 2015 by the American Society for Biochemistry and Molecular Biology Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - ABCG5 (G5) and ABCG8 (G8) form a sterol transporter that acts in liver and intestine to prevent accumulation of dietary sterols. Mutations in either G5 or G8 cause sitosterolemia, a recessive disorder characterized by sterol accumulation and premature coronary atherosclerosis. Hepatic G5G8 mediates cholesterol excretion into bile, but the function and relative importance of intestinal G5G8 has not been defi ned. To determine the role of intestinal G5G8, we developed liver-specifi c (L- G5G8 -/- ), intestinespecifi c ( I-G5G8 -/- ), and total ( G5G8 -/- ) KO mice. Tissue levels of sitosterol, the most abundant plant sterol, were >90-fold higher in G5G8 -/- mice than in WT animals. Expression of G5G8 only in intestine or only in liver decreased tissue sterol levels by 90% when compared with G5G8 -/- animals. Biliary sterol secretion was reduced in L-G5G8 -/- and G5G8 -/- mice, but not in I-G5G8 -/- mice. Conversely, absorption of plant sterols was increased in I- G5G8 -/- and G5G8 -/- mice, but not in L- G5G8 -/- mice. Reverse cholesterol transport, as assessed from the fraction of intravenously administered 3H-cholesterol that appeared in feces, was reduced in G5G8 -/- , I-G5G8 -/- , and L- G5G8 -/- mice. Thus, G5G8 expression in both the liver and intestine protects animals from sterol accumulation, and intestinal G5G8 contributes to extrahepatic cholesterol effl ux in mice. -Wang, J., M. A. Mitsche, D. Lütjohann, J. C. Cohen, X-S. Xie, and H. H. Hobbs. Relative roles of ABCG5/ABCG8 in liver and intestine. J. Lipid Res.
AB - ABCG5 (G5) and ABCG8 (G8) form a sterol transporter that acts in liver and intestine to prevent accumulation of dietary sterols. Mutations in either G5 or G8 cause sitosterolemia, a recessive disorder characterized by sterol accumulation and premature coronary atherosclerosis. Hepatic G5G8 mediates cholesterol excretion into bile, but the function and relative importance of intestinal G5G8 has not been defi ned. To determine the role of intestinal G5G8, we developed liver-specifi c (L- G5G8 -/- ), intestinespecifi c ( I-G5G8 -/- ), and total ( G5G8 -/- ) KO mice. Tissue levels of sitosterol, the most abundant plant sterol, were >90-fold higher in G5G8 -/- mice than in WT animals. Expression of G5G8 only in intestine or only in liver decreased tissue sterol levels by 90% when compared with G5G8 -/- animals. Biliary sterol secretion was reduced in L-G5G8 -/- and G5G8 -/- mice, but not in I-G5G8 -/- mice. Conversely, absorption of plant sterols was increased in I- G5G8 -/- and G5G8 -/- mice, but not in L- G5G8 -/- mice. Reverse cholesterol transport, as assessed from the fraction of intravenously administered 3H-cholesterol that appeared in feces, was reduced in G5G8 -/- , I-G5G8 -/- , and L- G5G8 -/- mice. Thus, G5G8 expression in both the liver and intestine protects animals from sterol accumulation, and intestinal G5G8 contributes to extrahepatic cholesterol effl ux in mice. -Wang, J., M. A. Mitsche, D. Lütjohann, J. C. Cohen, X-S. Xie, and H. H. Hobbs. Relative roles of ABCG5/ABCG8 in liver and intestine. J. Lipid Res.
KW - Bile
KW - Cholesterol/absorption
KW - Sterols
KW - Transport
UR - http://www.scopus.com/inward/record.url?scp=84921833435&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921833435&partnerID=8YFLogxK
U2 - 10.1194/jlr.M054544
DO - 10.1194/jlr.M054544
M3 - Article
C2 - 25378657
AN - SCOPUS:84921833435
SN - 0022-2275
VL - 56
SP - 319
EP - 330
JO - Journal of lipid research
JF - Journal of lipid research
IS - 2
ER -