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Adipose tissue gene expression in patients with a loss of function mutation in the leptin receptor

International Journal of Obesity volume 26, pages 1533–1538 (2002)Cite this article

Abstract

BACKGROUND: In order to maintain body weight regulation, leptin directly or indirectly signals nutritional changes to key organs, but little is known about its target genes in human adipose tissue. Leptin receptor loss of function is a unique way to explore the role of leptin in the regulation of adipose tissue.

OBJECTIVE: We studied the consequences of the absence of leptin signaling on adipocyte gene expression in two girls with a mutation in the leptin receptor. The expression levels of the ob gene and adipocyte transcription factors (SREBP1c, C/EPBα, β, PPARγ1, γ2) were quantified by RT-PCR in subcutaneous adipose tissue of these patients and of 10 morbidly obese women.

RESULTS: Ob mRNA levels in subjects lacking the leptin receptor were not overexpressed but were in the range that could be expected from their BMI (58 and 26 amol/µg total mRNA, range in obese women: 26–69). Expression of the five transcription factors was also in the same range in the affected patients and in morbidly obese women (7.7 and 6.8 amol/µg total mRNA, range: 2.2–9.4 for SREBP1c, 159 and 51 range: 51–406 for C/EPBα, 6.1 and 3.3 range: 2.4–24.8 for C/EPBβ, 16.7 and 27.4 range: 9.4–29.7 for PPARγ1 and 1.7 and 5.4 amol/µg total mRNA range: 1.7–8.8 for PPARγ2). Significant correlation was found between the mRNA levels of leptin and PPARγ2 and leptin and C/EBPα whereas no correlation was observed between leptin and SREBP1c, PPARγ1, or C/EBPβ mRNA levels.

CONCLUSION: In patients lacking leptin signaling, the fact that ob gene expression is adequately adapted to their body fat mass argues against a direct negative feedback loop in the regulation of leptin expression in humans. The normal expression of several transcription factors, known to be dependent of the nutritional status, suggests that leptin is not a major contributor of their in vivo transcriptional regulation in human adipose tissue.

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Acknowledgements

We gratefully thank Michèle Guerre-Millo (Inserm U465) for her accurate help while writing this manuscript and Najibal Lahlou for leptin measurements. Christian Vaisse contributed to the genetic characterization of the two leptin receptor deficient patients (CNRS UPRESA 8090). This work was supported by the Direction de la Recherche Clinique/Assistance Publique-Hopitaux de Paris and the Programme Hospitalier de Recherche Clinique (AOM 96088). Karine Clément is funded by Servier Research Institute (IRIS).

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Authors and Affiliations

  1. Equipe d'Accueil 3502 Université Paris VI et Service de Nutrition, Hôtel-Dieu, Formation Associée Claude Bernard, Paris, France

    K Clément, V Pelloux, B Guy-Grand & A Basdevant

  2. INSERM U449, Faculté de Médecine RTH Laennee, Lyon, France

    N Vega, M Laville & H Vidal

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  1. K Clément
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  2. N Vega
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  4. V Pelloux
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  6. A Basdevant
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  7. H Vidal
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Correspondence to K Clément.

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Clément, K., Vega, N., Laville, M. et al. Adipose tissue gene expression in patients with a loss of function mutation in the leptin receptor. Int J Obes 26, 1533–1538 (2002). https://doi.org/10.1038/sj.ijo.0802180

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