Background Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7 alpha-hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7 alpha-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 7 alpha-hydroxylase and related nuclear receptors and co-activators were assayed by quantitative real-time RT-PCR. Serum levels of 7 alpha-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 7 alpha-hydroxy-4-cholesten-3-one and with cholesterol 7 alpha-hydroxylase mRNA levels (r = -0.44 and r = -0.45 on a semi-log scale, respectively, P < 0.05). Among different nuclear factors, cholesterol 7 alpha-hydroxylase mRNA best correlated with hepatocyte nuclear factor-4 (r = 0.55 on a log scale, P < 0.05); hepatocyte nuclear factor-4 levels were also inversely correlated with age (r = -0.64 on a semi-log scale, P < 0.05). Age was inversely correlated with serum insulin-like growth factor-I levels, which were directly correlated with hepatocyte nuclear factor-4 and cholesterol 7 alpha-hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7 alpha-hydroxylase was observed. Conclusions Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor-4 and consequently of cholesterol 7 alpha-hydroxylase. Age-related modifications of the growth hormone/insulin-like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age-related modifications of cholesterol metabolism.
Citazione: | Bertolotti, M., Gabbi, C., Anzivino, C., Crestani, M., Mitro, N., Del Puppo, M., et al. (2007). Age-related changes in bile acid synthesis and hepatic nuclear receptor expression. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 37(6), 501-508. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Titolo: | Age-related changes in bile acid synthesis and hepatic nuclear receptor expression |
Autori: | 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 |
Autori: | |
Data di pubblicazione: | giu-2007 |
Lingua: | English |
Rivista: | EUROPEAN JOURNAL OF CLINICAL INVESTIGATION |
Digital Object Identifier (DOI): | 10.1111/j.1365-2362.2007.01808.x |
Appare nelle tipologie: | 01 - Articolo su rivista |