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Adipocyte and Cell Biology

Impaired atrial natriuretic peptide-mediated lipolysis in obesity

International Journal of Obesity volume 40, pages 714–720 (2016)Cite this article

Subjects

Abstract

Background:

Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered.

Methods:

Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis.

Results:

In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men.

Conclusions:

ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.

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Acknowledgements

We are grateful for the excellent technical assistance provided by Ms Yvonne Widlund, Ms Katarina Hertel, Ms Britt-Marie Leijonhufvud, Ms Elisabeth Dungner, Ms Eva Sjölin, Ms Kerstin Wåhlén and Ms Gaby Åström. This study was supported by grants from the Swedish Research Council, The Swedish Diabetes Foundation, the NovoNordisk Foundation, CIMED, the Diabetes Program at Karolinska Institutet, Astra-Zeneca, EFSD/Lilly and INSERM and the Erling-Persson Family Foundation. DL is a member of Institut Universitaire de France.

Author contributions

MR and PA conceived the study and wrote the first version of the manuscript, which was then read and approved by all coauthors. AT recruited the obese subjects in cohort 1, which were phenotyped by MR and PA. JB and PP performed the protein analyses. HG performed the bioinformatic analyses. DL, MC and CM performed and analyzed the microdialysis experiments in cohort 2. Statistical analyses were performed by MR. MR is the guarantor for the present work

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Authors and Affiliations

  1. Department of Medicine-H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    M Rydén, J Bäckdahl, P Petrus & P Arner

  2. Department of Surgery, Karolinska Institutet, Ersta Hospital, Stockholm, Sweden

    A Thorell

  3. Department of of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

    H Gao

  4. INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France

    M Coue, D Langin & C Moro

  5. University of Toulouse, UMR1048, Paul Sabatier University, France

    M Coue, D Langin & C Moro

  6. Department of Clinical Biochemistry, Toulouse University Hospitals, Toulouse, France

    D Langin

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  1. M Rydén
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Correspondence to M Rydén.

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Rydén, M., Bäckdahl, J., Petrus, P. et al. Impaired atrial natriuretic peptide-mediated lipolysis in obesity. Int J Obes 40, 714–720 (2016). https://doi.org/10.1038/ijo.2015.222

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  • DOI: https://doi.org/10.1038/ijo.2015.222

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