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Vaittinen, M., Ilha, M., Herbers, E., Wagner, A., Virtanen, K. A., Pietiläinen, K. H., Pirinen, E., & Pihlajamäki, J. (2023). Liraglutide demonstrates a therapeutic effect on mitochondrial dysfunction in human SGBS adipocytes in vitro. In Diabetes Research and Clinical Practice (Vol. 199, p. 110635). Elsevier BV. https://doi.org/10.1016/j.diabres.2023.110635.

Liraglutide demonstrates a therapeutic effect on mitochondrial dysfunction in human SGBS adipocytes in vitro

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Author: Vaittinen, Maija1; Ilha, Mariana1; Herbers, Elena2;
Organizations: 1Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
2Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland
3Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00290 Helsinki, Finland
4Research Unit for Internal Medicine, Faculty of Medicine, University of Oulu, FIN-90220 Oulu, Finland
5Department of Medicine, Endocrinology, and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
6Turku PET Centre, Turku University Hospital, Turku, Finland
7Obesity Center, Abdominal Center, Helsinki University Hospital and University of Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe20231024141167
Language: English
Published: Elsevier, 2023
Publish Date: 2023-10-24
Description:

Abstract

Aims: Liraglutide (LG), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been shown to improve white adipose tissue mitochondrial metabolism in mice but not in human adipocytes. Therefore, we explored whether LG has therapeutic efficacy in mitochondrial dysfunction in human adipocytes in vitro.

Methods: We tested the effects of short-term (ST-LG: 24 h) and long-term (LT-LG: D0-15 days) treatments in human SGBS adipocytes on mitochondrial respiration, mRNA and protein expression. GLP-1R inhibition was investigated by the co-treatment of GLP-1R inhibitor, exendin 9–39 (Ex9-39) and ST-LG treatment. We also explored the ability of ST-LG to alleviate mitochondrial dysfunction induced by tumor necrosis factor-alpha (TNFα).

Results: LT-LG treatment induced the formation of smaller lipid droplets and increased the expression of genes related to lipolysis. Both ST-LG and LT-LG treatments promoted mitochondrial respiration. Additionally, LT-LG treatment increased the expression of a brown adipocyte marker, uncoupling protein 1 (UCP-1), and the markers of mitochondrial biogenesis. Interestingly, ST-LG rescued TNFα-induced defects in mitochondrial energy metabolism and inflammation in SGBS adipocytes.

Conclusions: LG stimulates mitochondrial respiration and biogenesis in human adipocytes, potentially via UCP-1-mediated adipocyte browning. Importantly, our study demonstrates for the first time that LG has a therapeutic potential on mitochondrial activity in human adipocytes.

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Series: Diabetes research and clinical practice
ISSN: 0168-8227
ISSN-E: 1872-8227
ISSN-L: 0168-8227
Volume: 199
Article number: 110635
DOI: 10.1016/j.diabres.2023.110635
OADOI: https://oadoi.org/10.1016/j.diabres.2023.110635
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Adipocyte
Browning
Glucagon-like peptide-1
Human
Liraglutide
Mitochondrial function
Article
Funding: This work was supported by the following fundings. MV: Academy of Finland; grant number 324494. KAV: Academy of Finland, grant numbers 314456, 335446. KHP: Academy of Finland, grant numbers 335443, 314383, 272376, 266286; Finnish Medical Foundation; Gyllenberg Foundation; Novo Nordisk Foundation, grant numbers NNF20OC0060547, NNF17OC0027, NF10OC1013354; Finnish Diabetes Research Foundation; University of Helsinki; Government Research Funds; Helsinki University Hospital. EP: Academy of Finland, grant numbers 335445, 314455, 336449; Finnish Medical Foundation. JP: Academy of Finland, grant numbers 335444 and 314454; Finnish Medical Foundation and Kuopio University Hospital (Government Research Funds 2005–2021).
Copyright information: © 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  https://creativecommons.org/licenses/by/4.0/