Relative roles of ABCG5/ABCG8 in liver and intestine

Abstract

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 defined. To determine the role of intestinal G5G8, we developed liver-specific (L-G5G8−/−), intestine-specific (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 efflux in mice.

Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet–induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles

“…Studies concerning Pctp −/− mice have found that body fat composition was increased in Pctp −/− mice [49,51]. The function of Abcg5 is to maintain sterol balance in vertebrates [52]. More studies are required to clarify the compounds in PTE that may activate Lpin-1, Pctp, and Abcg5 gene expression through directly interaction with PPARα.…”

ABCG5 and ABCG8 Gene Polymorphisms in Type 2 Diabetes Mellitus in the Turkish Population

“…The proteins encoded by the ABCG5 and ABCG8 genes located in head-to-head orientation on exon 13 of chromosome 2p21 are expressed in both the liver and intestine and function to regulate cholesterol re-excretion (7,8,19e21,26,27). ATP binding cassette proteins G5/G8 prevent accumulation of sterols, decrease sterol absorption in the intestine and increase sterol excretion from the liver into the bile (26,27). Mutations in either ABCG5 or ABCG8 transporters cause hyperabsorption and decreased biliary excretion of sterols, leading to sitosterolemia.…”

“…The samples were centrifuged for 10 minutes at 1.500 Âg at þ4 C, followed by the removal of serum and plasma and then were stored at e20 C. Fasting glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, lowdensity lipoprotein (LDL) cholesterol and very low-density lipoprotein (VLDL) cholesterol were determined in the study groups by standard laboratory methods in the Istanbul University and Haseki Training and Research hospitals (26,27). In addition, body mass index (BMI; weight in kilograms divided by the square of the height in meters) values were calculated and categorized according to World Health Organization recommendations.…”

Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone

“…ABCG5 and ABCG8 are expressed in the liver and small intestine, where they function to excrete sterols into bile and limit intestinal absorption of dietary plant sterols [9] . Genetic variation in ABCG5/8, simultaneously influence plasma and biliary cholesterol levels.…”