Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes

Zoltán Balogh, Gabriella Fóris, Gabriella Kónya, G. Paragh, Tamás Köbling, János T. Padra, Z. Sarang, György Paragh

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Leptin the cytokine-like hormone is involved not only in local inflammations, but it regulates cholesterol biosynthesis in human monocytes. Since, monocyte-membrane composition in obesity shows considerable difference from control cells, our aim was to elucidate the concentration dependence of the effect of leptin in OW monocytes, and the downstream signaling of high and low leptin concentrations. Control and OW monocytes were stimulated with leptin in the presence or absence of different inhibitors. Our results are as follows: a concentration-dependent biphasic effect could only be detected in control monocytes whereas in OW cells only elevated cholesterol synthesis was found. The signal pathway of 50ng/mL leptin stimulation involves Ca2+ signal, activation of PI3K, MAPK and HMG CoA reductase. In the 500ng/mL leptin-stimulated control monocytes the suppression of cholesterol synthesis was dependent on the Ca2+ signal, the H-7 sensitive cPKC and PI3K activation, whereas in OW monocytes only PI3K was involved in increased cholesterol synthesis. We conclude that leptin-signaling in OW monocytes is characterized by Ca2+ influx, abrogation of H-7 sensitive cPKC activation, and by PI3K mediated PKC activation.

Original languageEnglish
Pages (from-to)431-435
Number of pages5
JournalImmunobiology
Volume216
Issue number3
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Leptin
Monocytes
Obesity
Cholesterol
Phosphatidylinositol 3-Kinases
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Hydroxymethylglutaryl CoA Reductases
Hypercholesterolemia
Signal Transduction
Hormones
Cytokines
Inflammation
Membranes

Keywords

  • Cholesterol synthesis
  • Human monocytes
  • Leptin stimulation
  • Overweight
  • Proteinkinase isoforms
  • Signal pathway

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology

Cite this

Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes. / Balogh, Zoltán; Fóris, Gabriella; Kónya, Gabriella; Paragh, G.; Köbling, Tamás; Padra, János T.; Sarang, Z.; Paragh, György.

In: Immunobiology, Vol. 216, No. 3, 03.2011, p. 431-435.

Research output: Contribution to journalArticle

Balogh, Zoltán ; Fóris, Gabriella ; Kónya, Gabriella ; Paragh, G. ; Köbling, Tamás ; Padra, János T. ; Sarang, Z. ; Paragh, György. / Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes. In: Immunobiology. 2011 ; Vol. 216, No. 3. pp. 431-435.
@article{d8bbbc0c769a42009e80a9ae1e598210,
title = "Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes",
abstract = "Leptin the cytokine-like hormone is involved not only in local inflammations, but it regulates cholesterol biosynthesis in human monocytes. Since, monocyte-membrane composition in obesity shows considerable difference from control cells, our aim was to elucidate the concentration dependence of the effect of leptin in OW monocytes, and the downstream signaling of high and low leptin concentrations. Control and OW monocytes were stimulated with leptin in the presence or absence of different inhibitors. Our results are as follows: a concentration-dependent biphasic effect could only be detected in control monocytes whereas in OW cells only elevated cholesterol synthesis was found. The signal pathway of 50ng/mL leptin stimulation involves Ca2+ signal, activation of PI3K, MAPK and HMG CoA reductase. In the 500ng/mL leptin-stimulated control monocytes the suppression of cholesterol synthesis was dependent on the Ca2+ signal, the H-7 sensitive cPKC and PI3K activation, whereas in OW monocytes only PI3K was involved in increased cholesterol synthesis. We conclude that leptin-signaling in OW monocytes is characterized by Ca2+ influx, abrogation of H-7 sensitive cPKC activation, and by PI3K mediated PKC activation.",
keywords = "Cholesterol synthesis, Human monocytes, Leptin stimulation, Overweight, Proteinkinase isoforms, Signal pathway",
author = "Zolt{\'a}n Balogh and Gabriella F{\'o}ris and Gabriella K{\'o}nya and G. Paragh and Tam{\'a}s K{\"o}bling and Padra, {J{\'a}nos T.} and Z. Sarang and Gy{\"o}rgy Paragh",
year = "2011",
month = "3",
doi = "10.1016/j.imbio.2010.06.012",
language = "English",
volume = "216",
pages = "431--435",
journal = "Immunobiology",
issn = "0171-2985",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "3",

}

TY - JOUR

T1 - Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes

AU - Balogh, Zoltán

AU - Fóris, Gabriella

AU - Kónya, Gabriella

AU - Paragh, G.

AU - Köbling, Tamás

AU - Padra, János T.

AU - Sarang, Z.

AU - Paragh, György

PY - 2011/3

Y1 - 2011/3

N2 - Leptin the cytokine-like hormone is involved not only in local inflammations, but it regulates cholesterol biosynthesis in human monocytes. Since, monocyte-membrane composition in obesity shows considerable difference from control cells, our aim was to elucidate the concentration dependence of the effect of leptin in OW monocytes, and the downstream signaling of high and low leptin concentrations. Control and OW monocytes were stimulated with leptin in the presence or absence of different inhibitors. Our results are as follows: a concentration-dependent biphasic effect could only be detected in control monocytes whereas in OW cells only elevated cholesterol synthesis was found. The signal pathway of 50ng/mL leptin stimulation involves Ca2+ signal, activation of PI3K, MAPK and HMG CoA reductase. In the 500ng/mL leptin-stimulated control monocytes the suppression of cholesterol synthesis was dependent on the Ca2+ signal, the H-7 sensitive cPKC and PI3K activation, whereas in OW monocytes only PI3K was involved in increased cholesterol synthesis. We conclude that leptin-signaling in OW monocytes is characterized by Ca2+ influx, abrogation of H-7 sensitive cPKC activation, and by PI3K mediated PKC activation.

AB - Leptin the cytokine-like hormone is involved not only in local inflammations, but it regulates cholesterol biosynthesis in human monocytes. Since, monocyte-membrane composition in obesity shows considerable difference from control cells, our aim was to elucidate the concentration dependence of the effect of leptin in OW monocytes, and the downstream signaling of high and low leptin concentrations. Control and OW monocytes were stimulated with leptin in the presence or absence of different inhibitors. Our results are as follows: a concentration-dependent biphasic effect could only be detected in control monocytes whereas in OW cells only elevated cholesterol synthesis was found. The signal pathway of 50ng/mL leptin stimulation involves Ca2+ signal, activation of PI3K, MAPK and HMG CoA reductase. In the 500ng/mL leptin-stimulated control monocytes the suppression of cholesterol synthesis was dependent on the Ca2+ signal, the H-7 sensitive cPKC and PI3K activation, whereas in OW monocytes only PI3K was involved in increased cholesterol synthesis. We conclude that leptin-signaling in OW monocytes is characterized by Ca2+ influx, abrogation of H-7 sensitive cPKC activation, and by PI3K mediated PKC activation.

KW - Cholesterol synthesis

KW - Human monocytes

KW - Leptin stimulation

KW - Overweight

KW - Proteinkinase isoforms

KW - Signal pathway

UR - http://www.scopus.com/inward/record.url?scp=79251595017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251595017&partnerID=8YFLogxK

U2 - 10.1016/j.imbio.2010.06.012

DO - 10.1016/j.imbio.2010.06.012

M3 - Article

VL - 216

SP - 431

EP - 435

JO - Immunobiology

JF - Immunobiology

SN - 0171-2985

IS - 3

ER -