Leptin stimulates endogenous cholesterol synthesis in human monocytes: New role of an old player in atherosclerotic plaque formation. Leptin-induced increase in cholesterol synthesis

Béla Kosztáczky, Gabriella Fóris, György Paragh, Ildikó Seres, Emese Zsiros, Péter Koncsos, Zoltán Balogh, György Paragh

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The role of leptin in the pathomechanism of atherosclerosis, through its free radical generating ability is established. Its effect however, on the regulation of intracellular cholesterol synthesis has not been studied. The aim of the present study was to elucidate whether leptin influences endogenous cholesterol synthesis in monocytes. Furthermore, leptin signaling to HMG CoA reductase in control and hypercholesterolemic monocytes were compared. The in vitro effect of leptin was studied on freshly isolated human monocytes obtained from healthy control volunteers and patients with hypercholesterolemia. Our results can be summarized as follows: (1) Leptin is able to increase endogenous cholesterol synthesis in human monocytes in vitro. (2) The cholesterol synthesis increasing effect of the hormone is more pronounced in hypercholesterolemic monocytes with high basal cholesterol biosynthesis. (3) The leptin-induced Ca2+ signal was involved in the enhancement of HMG CoA reductase activation in monocytes from both controls and hypercholesterolemic patients. (4) In control monocytes the Ca2+ signal originated from intracellular pools, whereas in patients, Ca2+-influx and protein kinase C activation were found to be responsible for the leptin-effect. Mevalonate cycle inhibiting fluvastatin and 25-hydroxycholesterol decreased cholesterol production in leptin-stimulated monocytes. Our present study provides the first proof of the cholesterol synthesis enhancing effect of leptin through a statin-sensitive pathway in circulating monocytes. Furthermore our results suggest that leptin can be involved in the pathomechanism of atherosclerotic plaque formation also through its effect on cholesterol biosynthesis in monocytes.

Original languageEnglish
Pages (from-to)1637-1645
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume39
Issue number9
DOIs
Publication statusPublished - Jul 26 2007

Keywords

  • Atherosclerosis
  • Ca signal
  • HMG CoA reductase
  • Human monocytes
  • Leptin
  • Signal processing inositol trisphosphate

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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