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Cited by 7Mitochondrial Function and PathologyAdipose Tissue and MetabolismDiabetes Treatment and Management

Impact of GLP-1 receptor agonist versus omega-3 fatty acids supplement on obesity-induced alterations of mitochondrial respiration

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Jansen, Kirsten M., Dahdah, Norma, Gama-Perez, Pau, Schots, Pauke C., Larsen, Terje S., Garcia-Roves, Pablo M.·2023·Frontiers in Endocrinology
DOI 10.3389/fendo.2023.1098391PMC PMC10076843
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Abstract

Objective: To compare administration of the glucagon-like peptide-1 (GLP-1) analogue, exenatide, versus dietary supplementation with the omega-3 fatty acid-rich Calanus oil on obesity-induced alterations in mitochondrial respiration. Methods: Six-week-old female C57BL/6JOlaHSD mice were given high fat diet (HFD, 45% energy from fat) for 12 weeks to induce obesity. Thereafter, they were divided in three groups where one received exenatide (10 μg/kg/day) via subcutaneously implanted mini-osmotic pumps, a second group received 2% Calanus oil as dietary supplement, while the third group received HFD without any treatment. Animals were sacrificed after 8 weeks of treatment and tissues (skeletal muscle, liver, and white adipose tissue) were collected for measurement of mitochondrial respiratory activity by high-resolution respirometry, using an Oroboros Oxygraph-2k (Oroboros instruments, Innsbruck, Austria). Results: It was found that high-fat feeding led to a marked reduction of mitochondrial respiration in adipose tissue during all three states investigated – LEAK, OXPHOS and ETS. This response was to some extent attenuated by exenatide treatment, but not with Calanus oil treatment. High-fat feeding had no major effect on hepatic mitochondrial respiration, but exenatide treatment resulted in a significant increase in the various respiratory states in liver. Mitochondrial respiration in skeletal muscle was not significantly influenced by high-fat diet or any of the treatments. The precise evaluation of mitochondrial respiration considering absolute oxygen flux and ratios to assess flux control efficiency avoided misinterpretation of the results. Conclusions: Exenatide increased hepatic mitochondrial respiration in high-fat fed mice, but no clear beneficial effect was observed in skeletal muscle or fat tissue. Calanus oil did not negatively affect respiratory activity in these tissues, which maintains its potential as a dietary supplement, due to its previously reported benefits on cardiac function

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  • Jansen et al. concluded that mitochondrial respiration was not influenced by exenatide treatment in HFD-fed mice (neutral effect).

    “Overall, the authors concluded that mitochondrial respiration was not influenced by exenatide treatment.”

    From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [41]

    The Discussion conclusion says exenatide increased hepatic mitochondrial respiration in high-fat-fed mice, contrary to an overall neutral effect. It found no clear beneficial effect in skeletal muscle or fat tissue, but that narrower finding does not support saying mitochondrial respiration was not influenced by exenatide treatment overall. (LLM, conf=0.89)

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  • Jansen et al. was the only study to measure mitochondrial respiration using high-resolution respirometry (oxygraphy-2k system), the gold standard method for this investigation.

    “Importantly, this study was the only study to measure mitochondrial respiration using high‐resolution respirometry (oxygraphy‐2k system), the gold standard method for this investigation.”

    From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [41]

    The Materials and methods section (High-resolution respirometry; page unavailable) confirms that Jansen et al. measured mitochondrial respiration with high-resolution respirometry using an Oxygraph-2k system. Our copy does not establish that it was the only study to do so or characterize the method as the gold standard. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The majority of LEAK, OXPHOS and ETS respiration were not significantly different compared with HFD.

    “However, the majority of the LEAK respiration (O2 compensating for the lack of ATP synthesis), OXPHOS respiration (the NADH pathway) and electron transfer system (ETS) respiration were not significantly different when compared with the HFD.”

    From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [41]

  • Jansen et al. reported that flux control efficiency showed a significant decrease and maximum complex I activity decreased in HFD-fed mice supplemented with Exenatide.

    “They did however report that the flux control efficiency showed a significant decrease as well as the maximum complex I activity in HFD‐fed mice supplemented with Exenatide.”

    From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [41]

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Authors
Jansen, K. M., Dahdah, N., Gama-Perez, P., Schots, P. C., Larsen, T. S., & Garcia-Roves, P. M.
Affiliations
  • UiT The Arctic University of Norway (NO)
  • Institut d'Investigació Biomédica de Bellvitge (ES)
Corresponding author
Larsen, Terje S.
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2023-03-23
Volume
14
Pages
1098391-1098391
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2023.1098391
PMC
PMC10076843
OpenAlex
W4360616568
Cited by
7
References
7
Citations by year
2026: 3 · 2025: 3 · 2024: 1
FWCI
0.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • Generalitat de Catalunya
  • Helse Nord RHF (HNF-1341-17)
  • Agència de Gestió d'Ajuts Universitaris i de Recerca (2017-SGR-204)
  • Instituto de Salud Carlos III (AGAUR 2017, PI15/00701, Grant PI15/00701)
  • European Regional Development Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
exenatide, GLP-1 receptor agonists, omega-3 fatty acids, mitochondrial respiration, obesity, high-fat diet, liver mitochondria, white adipose tissue, skeletal muscle, dietary supplementation
MeSH terms
Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Female, Mice, Inbred C57BL, Obesity, Respiration, Fatty Acids, Omega-3, Dietary Supplements, Mice

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