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  • SCImago Journal Rank (SJR):0,195
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Clin Invest Arterioscl 2002;14:67-73 - DOI: 10.1016/S0214-9168(02)78828-1
La leptina reduce los valores de ARNm del receptor activado por proliferadores peroxisómicos γ en macrófagos humanos
Leptin down-regulates PPAR γ in human macrophages
A. Cabrero, , M. Cubero, G. Llaverías, J.C. Laguna, M. Vázquez Carrera
Unidad de Farmacología. Departamento de Farmacología y Química Terapéutica. Facultad de Farmacia.Universidad de Barcelona. Barcelona

Increased leptin levels are associated with cardiovascular disease in obesity although the mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPAR γ) is a key regulator of macrophage lipid metabolism and its activation by thiazolidinediones protects against atherosclerosis. The aim of this study was to assess the effects of human recombinant leptin on PPAR γ mRNA levels in primary human macrophages and macrophage-derived foam cells

Material and methods

Human monocytes were isolated by gradient density centrifugation from buffy coats of human donors. The mononuclear cells were then incubated with heat-inactivated human serum and on day 10 completely differentiated to macrophages. After that, differentiated macrophages were lipid-loaded during a 48-hour incubation with 150 μg/ml acetyl-LDL. Relative levels of specific mRNAs were assessed by RT-PCR. Results are expressed as means ± SD of 3 experiments


In human-derived macrophages leptin treatment (100 ng/ml) for 24 hours caused a 41% reduction (p < 0.01) in PPAR γ transcript levels. This fall was accompanied by a reduction in the mRNA expression of carnitine palmitoyltransferase (CPT-I) (36%, p < 0.05) and ABCA1 (62%, p < 0.05), whereas CD36 mRNA reduction (34%) was not significant. In macrophage-derived foam cells, leptin at 20 ng/mL reduced PPAR γ mRNA levels a 33% (p < 0.01) and CPT-I a 27% (p ≤ 0.05). At this concentration, leptin did not modify the expression of either ABCA1 or CD36


We propose that the reduction of PPAR γ expression in both macrophages and foam cells may be one of the factors linking high leptin levels and cardiovascular disease

Palabras clave
Leptina, Macrófagos, Células espumosas, PPAR γ, ABCA1, CD36
Key words
Leptin, Macrophage, Foam cell, PPAR γ, ABCA1, CD36
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Correspondencia: Unitat de Farmacologia. Facultat de Farmàcia. Universitat de Barcelona. Diagonal, 643. 08028 Barcelona (A. Cabrero mvaz@farmacia.far.ub.es)
Copyright © 2002. Sociedad Española de Arteriosclerosis y Elsevier España, S.L.