Age-related changes in bile acid synthesis and hepatic nuclear receptor expression

• Published in: European journal of clinical investigation 2007-06, Vol.37 (6), p.501-508
• Main Authors: Bertolotti, M., Gabbi, C., Anzivino, C., Crestani, M., Mitro, N., Del Puppo, M., Godio, C., De Fabiani, E., Macchioni, D., Carulli, L., Rossi, A., Ricchi, M., Loria, P., Carulli, N.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Ageing; Aging - metabolism; bile acid synthesis; Bile Acids and Salts - biosynthesis; Biological and medical sciences; Cholesterol 7-alpha-Hydroxylase - metabolism; cholesterol 7α-hydroxylase; Disorders of blood lipids. Hyperlipoproteinemia; Female; General aspects; Hepatocyte Nuclear Factor 4 - analysis; Hepatocyte Nuclear Factor 4 - genetics; hepatocyte nuclear factor-4; Humans; insulin-like growth factor-I; Lipogenesis; Liver - enzymology; Male; Medical sciences; Metabolic diseases; Middle Aged; nuclear receptors; Receptors, Cytoplasmic and Nuclear
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2007.01808.x

Background  Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7α‐hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7α‐hydroxylase and related nuclear receptor expression in human livers. Design  Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7α‐hydroxylase and related nuclear receptors and co‐activators were assayed by quantitative real‐time RT‐PCR. Serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one, a marker of bile acid synthesis, were assayed by gas‐liquid chromatography:mass spectrometry. Results  Ageing was inversely correlated with serum 7α‐hydroxy‐4‐cholesten‐3‐one and with cholesterol 7α‐hydroxylase mRNA levels (r = –0·44 and r = −0·45 on a semi‐log scale, respectively, P