A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds
Tekijät: Wagner, Anita; Lautaoja-Kivipelto, Juulia H.; Pehkonen, Kalle; Hassinen, Antti; Kuusela, Minna; Röttger, Lisa; Herbers, Elena; Ioannidou, Anna; Mädler, Sophia; Rothenaigner, Ina; Srinivasan, Soumya; Laasonen, Sini; Rahman, M. Tanvir; Elomaa, Pinja; Kortetjärvi, Saija; Olsson, Anneli; Ukkola, Olavi; Hadian, Kamyar; Mann, Matthias; Peltoniemi, Hilkka; Pietiläinen, Kirsi H.; Klingenspor, Martin; Virtanen, Kirsi A.; Hagberg, Carolina E.; Pirinen, Eija
Kustantaja: Elsevier BV
Julkaisuvuosi: 2026
Lehti: iScience
Artikkelin numero: 114480
Vuosikerta: 29
Numero: 2
eISSN: 2589-0042
DOI: https://doi.org/10.1016/j.isci.2025.114480
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1016/j.isci.2025.114480
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/515510477
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
Mitochondrial abnormalities drive subcutaneous white adipose tissue dysfunction in obesity, yet in vitro models to study adipocyte mitochondria remain limited. Here, we establish a human subcutaneous adipocyte spheroid model to characterize mitochondrial metabolism under obesity-relevant conditions and drug exposure. Human preadipocyte spheroids were differentiated in ultra-low attachment plates for 3 weeks using thiazolidinedione-free medium. Matrigel embedding was incorporated into the protocol as it promoted mitochondrial network and respiration compared to scaffold-free conditions. Differentiated spheroids showed increased lipid accumulation, adipogenic gene expression, mitochondrial respiration, adiponectin secretion, and hormonal responsiveness. Lipid mixture administration during differentiation induced metabolic disturbances, including mitochondrial respiration failure, alongside increased mitochondrial biogenesis. Post-differentiation treatment with rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, improved mitochondrial bioenergetics and adiponectin secretion in lipid mixture-administered adipocyte spheroids. Our model enables precise measurement of adipocyte mitochondria metabolism, providing a platform for mitochondria-focused research and drug discovery in obesity.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
This work was supported by the Academy of Finland/Research Council of Finland (335445, 335446, 314455, 314456, 266286, 272376, 314383, and 335443), Finnish Medical Foundation, Finnish Diabetes Research Foundation, Suorsa Foundation, Gyllenberg Foundation, Novo Nordisk Foundation (NNF20OC0060547, NNF17OC0027232, NNF10OC1013354), Paulo Foundation, Sigrid Jusélius Foundation, Government Research Funds, Research Council of Finland Profi6 funding (336449) awarded to the University of Oulu. C.E.H. was supported by Karolinska Institutet (2-1062/2018 and 2-189/2022) and Diabetes Wellness Sweden (DWPG-2022-0032). A.W. was awarded a young investigator start-up project funded by the Deutsche Forschungsgemeinschaft (CRC-TRR333 BATenergy). Open access was funded by Helsinki University Library.
