Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 129, Issue 12, Pages 722-727Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2008.09.010
Keywords
Ageing; Caloric restriction; Hypercholesterolemia; HMG-CoAR; Omega-3
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Funding
- Ricerca Corrente 2006 2007 from the University of Roma Tre
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Intracellular concentration of cholesterol is regulated by the balance between endogenous synthesis and exogenous uptake; endogenous synthesis is subject to feedback control of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase activity, while the exogenous supply is mainly controlled by the modulation of the low-density lipoprotein receptor. During ageing, hepatic lipid modifications occur and caloric restriction are able to prevent these changes. So, the aim of this work was to evaluate the mechanisms underlying the effect exerted both by caloric restrictions and by a diet enriched with Omega-3 fatty acids, on the cholesterol plasma levels during ageing, by Studying the regulation of the protein involved in cholesterol homeostasis maintenance. Livers from diet restricted and Omega-3 supplemented diet fed 24-month-old rat Were used to analyze, the protein complex of cholesterol homeostasis maintenance and those ones that are able to modulate 3-hydroxy-3-methyl-glutaryl-CoA reductase. The data obtained demonstrate that both caloric restriction and Omega-3 supplemented diets are able to prevent hypercholesterolemia, by regulating HMG-CoAR activation state by controlling ROS production and p38 phosphorylation. Moreover also the age-dependent loss of LDLr membrane exposition is prevented. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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