Diet-induced Lipid Accumulation in Liver Enhances ATP-binding Cassette Transporter g5/g8 Expression in Bile Canaliculi

Abstract

The ATP-binding cassette half-transporters Abcg5 and Abcg8 promote the secretion of neutral sterols into bile. Studies have demonstrated the diet-induced expression of these transporters in liver, but precisely where this occurs remains to be elucidated. This study investigated the changes in the expression of these transporters in bile canaliculi in cholesterol-loaded livers. Mice were fed either a standard (SD) diet or a high-fat and high-sucrose (HF/HS) diet for 3 weeks. Bile canaliculi proteins and cryosections were prepared from the liver, and the protein levels and distribution of Abcg5/Abcg8 were determined. The high-calorie diet induced a marked accumulation of lipids in mouse liver. Protein levels of Abcg5 and Abcg8 in bile canaliculi were significantly increased by the HF/HS diet compared to the SD diet. No significant differences in Abca1, Abcb4 (Mdr2), Abcb11 (Bsep), or Abcc2 (Mrp2) levels were observed. Immunohistochemical analyses confirmed that these increases occurred in bile canaliculi. These results suggest that diet-induced lipid loading of the liver causes a significant increase in the expression of Abcg5 and Abcg8 in bile canaliculi.