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Adipocyte and Cell Biology

Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor

International Journal of Obesity volume 41, pages 1547–1555 (2017)Cite this article

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Abstract

Background:

Growth hormone-releasing hormone (GHRH) has a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism.

Objectives:

To determine whether GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analyze the effects of GHRH on human adipocyte differentiation and lipolysis.

Methods:

GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects. Human mesenchymal stem cells (HMSC) were differentiated to adipocytes with GHRH (10−14–10−8 M). Adipocyte differentiation, lipolysis and gene expression were measured and the effect of GH-R silencing was determined.

Results:

Mature adipocytes from morbidly obese subjects showed a higher expression of GHRH and GH-R, and a lower expression of GHRH-R and GH than non-obese subjects (P<0.05). A total of 10−14–10−10 M GHRH induced an inhibition of lipid accumulation and PPAR-γ expression (P<0.05), and an increase in glycerol release and HSL expression (P<0.05) in human differentiated adipocytes. A total of 10−12–10−8 M GHRH decreased GHRH-R expression in human differentiated adipocytes (P<0.05). A total of 10−10–10−8 M GHRH increased GH and GH-R expression in human differentiated adipocytes (P<0.05). The effects of GHRH at 10−10 M on adipocyte differentiation and lipolysis were blocked when GH-R expression was silenced.

Conclusions:

GHRH and GHRH-R are expressed in human adipocytes and are negatively associated. GHRH at low doses may exert an anti-obesity effect by inhibiting HMSC differentiation in adipocytes and by increasing adipocyte lipolysis in an autocrine or paracrine pathway. These effects are mediated by GH and GH-R.

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Acknowledgements

CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM) are initiatives of ISCIII (Spain). Rodriguez-Pacheco F is supported by a fellowship from the Talent Hub program of the Consejería de Economia, Innovacion, Ciencia y Empresa de la Junta de Andalucía (TAHUB-042) (Spain). This work was supported in part by a grant from the Consejería de Economia, Innovacion, Ciencia y Empresa de la Junta de Andalucía (CTS-8081) ('Andalusia moves with Europe'). This study has been co-funded by FEDER funds.

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Authors and Affiliations

  1. Unidad de Gestión Clínica de Endocrinología y Nutrición/Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Málaga, Spain

    F Rodríguez-Pacheco, C Gutierrez-Repiso, S García-Serrano, S Valdes, M Gonzalo, G Rojo-Martínez & E García-Escobar

  2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Málaga, Spain

    S García-Serrano, S Valdes, G Rojo-Martínez & E García-Escobar

  3. Unidad de Gestión Clínica de Aparato Digestivo/Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain

    A Ho-Plagaro & E García-Fuentes

  4. ECAI de Genomica, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain

    J M Gómez-Zumaquero

  5. Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario, Málaga, Spain

    J Rivas-Becerra & C Montiel-Casado

  6. CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Málaga, Spain

    E García-Fuentes

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  1. F Rodríguez-Pacheco
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Correspondence to E García-Escobar or E García-Fuentes.

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Rodríguez-Pacheco, F., Gutierrez-Repiso, C., García-Serrano, S. et al. Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor. Int J Obes 41, 1547–1555 (2017). https://doi.org/10.1038/ijo.2017.145

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