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The Use of Stable and Radioactive Sterol Tracers as a Tool to Investigate Cholesterol Degradation to Bile Acids in Humans in Vivo
Divisone di Geriatria, Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Nuovo Ospedale Civile, Via Giardini 1355, Modena 41126, Italy
Dipartimento di Medicina Interna, Epatologia e Gastroenterologia, Università degli Studi di Milano, Ospedale San Paolo, Via Di Rudinì 8, Milano 20142, Italy
Dipartimento di Medicina Sperimentale, Università degli Studi di Milano Bicocca, Via Cadore 48, Monza 20052, Italy
* Author to whom correspondence should be addressed.
Received: 13 January 2012; in revised form: 3 February 2012 / Accepted: 8 February 2012 / Published: 16 February 2012
(This article belongs to the Special Issue Steroids
Abstract: Alterations of cholesterol homeostasis represent important risk factors for atherosclerosis and cardiovascular disease. Different clinical-experimental approaches have been devised to study the metabolism of cholesterol and particularly the synthesis of bile acids, its main catabolic products. Most evidence in humans has derived from studies utilizing the administration of labeled sterols; these have several advantages over in vitro assay of enzyme activity and expression, requiring an invasive procedure such as a liver biopsy, or the determination of fecal sterols, which is cumbersome and not commonly available. Pioneering evidence with administration of radioactive sterol derivatives has allowed to characterize the alterations of cholesterol metabolism and degradation in different situations, including spontaneous disease conditions, aging, and drug treatment. Along with the classical isotope dilution methodology, other approaches were proposed, among which isotope release following radioactive substrate administration. More recently, stable isotope studies have allowed to overcome radioactivity exposure. Isotope enrichment studies during tracer infusion has allowed to characterize changes in the degradation of cholesterol via the “classical” and the “alternative” pathways of bile acid synthesis. Evidence brought by tracer studies in vivo, summarized here, provides an exceptional tool for the investigation of sterol metabolism, and integrate the studies in vitro on human tissue.
Keywords: bile acid kinetics; cholesterol degradation; human studies in vivo; sterol tracers
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Bertolotti, M.; Crosignani, A.; Del Puppo, M. The Use of Stable and Radioactive Sterol Tracers as a Tool to Investigate Cholesterol Degradation to Bile Acids in Humans in Vivo. Molecules 2012, 17, 1939-1968.
Bertolotti M, Crosignani A, Del Puppo M. The Use of Stable and Radioactive Sterol Tracers as a Tool to Investigate Cholesterol Degradation to Bile Acids in Humans in Vivo. Molecules. 2012; 17(2):1939-1968.
Bertolotti, Marco; Crosignani, Andrea; Del Puppo, Marina. 2012. "The Use of Stable and Radioactive Sterol Tracers as a Tool to Investigate Cholesterol Degradation to Bile Acids in Humans in Vivo." Molecules 17, no. 2: 1939-1968.