Diminished gene expression of ileal apical sodium bile acid transporter explains impaired absorption of bile acid in patients with hypertriglyceridemia.
Patients with type IV hyperlipoproteinemia, particularly those with familial hypertriglyceridemia (FHT), have impaired absorption of bile acid, a defect that may contribute to the hypertriglyceridemia ( J. Lipid Res. 1995. 36: 96;-107). To determine whether this absorption defect is a result of abnormal expression of the ileal apical sodium bile acid transporter (ASBT) gene, we biopsied the terminal ileum at colonoscopy in 28 subjects, 13 with hypertriglyceridemia and 15 control subjects. Of the 13 hypertriglyceridemic subjects, 10 had lipid profiles compatible with FHT (elevated very low density lipoprotein [VLDL] triglycerides with normal LDL cholesterol). ASBT mRNA levels were measured in these biopsies by RNase protection assay, using glyceraldehyde dehydrogenase mRNA as a reference. ASBT protein was quantitated by Western blotting with an antibody to the carboxy-terminal 20 amino acids of the protein. The mean +/- SEM ASBT mRNA level in the control group was 205.7 +/- 19.9 (arbitrary units) compared with 138. 7 +/- 19.1 for all 13 hypertriglyceridemics (P = 0.03) and 141.7 +/- 20.8 in the 10 FHT patients (P = 0.05). Commensurate with these mRNA levels, the mean ASBT protein level in the control group was 126.2 +/- 22.6 versus 58.8 +/- 13.8 in hypertriglyceridemics (P = 0.02) and 61.8 +/- 15.2 in the FHT patients (P = 0.05). We conclude that impaired absorption of bile acid in type IV hypertriglyceridemia results from diminished expression of the ASBT gene in terminal ileum.
Duane
W C
WC
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.
Hartich
L A
LA
Bartman
A E
AE
Ho
S B
SB
D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism*; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003113:Colonoscopy; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D029363:Organic Anion Transporters, Sodium-Dependent; D014176:Protein Biosynthesis; D027981:Symporters; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; D014280:Triglycerides; C071908:sodium-bile acid cotransporter; D002784:Cholesterol