Decreased activity of lecithin:cholesterol acyltransferase and hepatic lipase in chronic hypothyroid rats: Implications for reverse cholesterol transport

  • Martha Franco
  • Graciela Castro
  • Luis Romero
  • Juan Carlos Regalado
  • Claudia Huesca-Gómez
  • Serafín Ramírez
  • Oscar Peréz-Méndez
  • Aida Medina
  • Carlos Posadas-Romero
  • Luis F. Montaño
Part of the Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease book series (DMCB, volume 41)

Abstract

Chronic hypothyroidism is frequently associated with atherosclerosis due to increased cholesterol plasma levels; nevertheless, the contribution of impaired reverse cholesterol transport (RCT) in this process has not been completely elucidated. The aim of this study was to evaluate the effect of thyroidectomy (Htx) upon the main stages of RCT in rats. Plasma lipid alterations induced by thyroidectomy showed a slight, but significant, reduction of total plasma triglycerides, a 300% increase of LDLcholesterol and a 25% decrease in HDL-cholesterol compared to control rats. We evaluated the first stage of RCT determining 3H-cholesterol efflux in Fu5AH cells. The capacity of HDL obtained from Htx rats to promote cholesterol efflux was similar to that of controls. Lecithin:cholesterol acyltransferase (LCAT) activity, the second stage and the driving force of RCT was 30% lower in Htx animals compared to controls, as determined by reconstituted HDL used as an external substrate. Lipoproteins are remodeled by hepatic lipase; the mean activity of this enzyme in postheparin plasma of Htx animals was reduced by 30% compared to controls, thus suggesting an impaired HDL remodeling by this enzyme in the hypothyroid status. In contrast, lipoprotein lipase activity in the Htx group was unchanged. In summary, this study demonstrates that chronic hypothyroidism in the rat induced an impaired RCT mainly at the cholesterol esterification, and HDL remodeling mediated by hepatic lipase. The latter probably results in an abnormal HDL structure, i.e. phospholipid enrichment, which contributes to decrease HDLapo AI fractional catabolic rates. (Mol Cell Biochem246:51-56, 2003)

Key words

reverse cholesterol transport cholesterol efflux high-density lipoproteins lecithin:cholesterol acyltranferase hepatic lipase hypothyroidism 

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Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Martha Franco
    • 1
  • Graciela Castro
    • 2
  • Luis Romero
    • 3
  • Juan Carlos Regalado
    • 3
  • Claudia Huesca-Gómez
    • 3
  • Serafín Ramírez
    • 3
  • Oscar Peréz-Méndez
    • 3
  • Aida Medina
    • 4
  • Carlos Posadas-Romero
    • 4
  • Luis F. Montaño
    • 5
  1. 1.Department of NephrologyInstituto Nacional de Cardiología ‘Ignacio Chávez’MéxicoFrance
  2. 2.Institut Pasteur de LilleAtherosclerosis and INSERMLilleFrance
  3. 3.Department of PhysiologyInstituto Nacional de Cardiología ‘Ignacio Chávez’MéxicoFrance
  4. 4.Department of EndocrinologyInstituto Nacional de Cardiología ‘Ignacio Chávez’MéxicoFrance
  5. 5.Department of Cellular BiologyInstituto Nacional de Cardiología ‘Ignacio Chávez’MéxicoFrance

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