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Adipocyte and Cell Biology

Peripherally administered melanocortins induce mice fat browning and prevent obesity

International Journal of Obesity volume 43, pages 1058–1069 (2019)Cite this article

Subjects

Abstract

Background/objectives

The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype.

Methods

The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles.

Results

Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis.

Conclusions

This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.

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Funding

This work was financially supported by FCT/MEC (PIDDAC) and FEDER–Fundo Europeu de Desenvolvimento Regional, COMPETE 2020–Programa Operacional Competitividade e Internacionalização (PTDC/BIM-MET/2123/2014) and Tanita Healthy Weight Community Trust. Parts of this work were supported by a grant from FCT to the Research Center in Physical Activity, Health and Leisure, UID/DTP/00617/2013 and PTDC/DTP-DES/7087/2014 - POCI-01-0145-FEDER-016690. ARR (SFRH/BPD/92868/2013) and SRR (SFRH/BD/89807/2012) are supported by FCT.

Author contributions

ARR and MJS performed the majority of the in vivo and in vitro experiments. SRR, IOG, and JM provided technical assistance in the oxygen consumption measurements. CC performed the subcutaneous implantation of osmotic mini-pumps in DIO mice. DN and HA contributed to experimental design and actively participated in the revision of the manuscript. ARR and AMG conceived the project, designed the experiments, analyzed the data, and wrote the manuscript with the input from the other authors.

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Authors and Affiliations

  1. Departamento de Biomedicina – Unidade de Biologia Experimental, Faculdade de Medicina do Porto; IBMC – Instituto de Biologia Molecular e Celular and I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-319, Porto, Portugal

    Adriana R. Rodrigues, Maria J. Salazar, Célia Cruz, Delminda Neves, Henrique Almeida & Alexandra M. Gouveia

  2. CIAFEL – Centro de Investigação em Atividade Física, Saúde e Lazer; LaMetEx – Laboratory of Metabolism and Exercise, Faculdade de Desporto da Universidade do Porto, 4200-319, Porto, Portugal

    Sílvia Rocha-Rodrigues, Inês O. Gonçalves & José Magalhães

  3. Escola Superior de Desporto e Lazer – Instituto Politécnico de Viana do Castelo, Viana do Castelo, Portugal

    Sílvia Rocha-Rodrigues

  4. Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto, 4200-319, Porto, Portugal

    Alexandra M. Gouveia

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  1. Adriana R. Rodrigues
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Correspondence to Alexandra M. Gouveia.

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Rodrigues, A.R., Salazar, M.J., Rocha-Rodrigues, S. et al. Peripherally administered melanocortins induce mice fat browning and prevent obesity. Int J Obes 43, 1058–1069 (2019). https://doi.org/10.1038/s41366-018-0155-5

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