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Wagner, A.* ; Lautaoja-Kivipelto, J.H.* ; Pehkonen, K.* ; Hassinen, A.* ; Kuusela, M.* ; Röttger, L.* ; Herbers, E.* ; Ioannidou, A.* ; Mädler, S.* ; Rothenaigner, I. ; Srinivasan, S.* ; Laasonen, S.* ; Rahman, M.T.* ; Elomaa, P.* ; Kortetjärvi, S.* ; Olsson, A.* ; Ukkola, O.* ; Hadian, K. ; Mann, M.* ; Peltoniemi, H.* ; Pietiläinen, K.H.* ; Klingenspor, M.* ; Virtanen, K.A.* ; Hagberg, C.E.* ; Pirinen, E.*

In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds.

iScience 29:114480 (2026)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Adipocyte ; Human Metabolism ; Lipid ; Mitochondria ; Obesity ; Spheroid; Adipose-tissue; Therapeutic Target; Ppar-gamma; Differentiation; Adiponectin; Biogenesis

ISSN (print) / ISBN 2589-0042

e-ISSN 2589-0042

Journal iScience

Quellenangaben Volume: 29, Issue: 2, Article Number: 114480

Publisher Elsevier

Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis

Reviewing status Peer reviewed

Institute(s) Research Unit Signaling and Translation (SAT)

Grants Helsinki University Library
Finnish Medical Foundation
Academy of Finland/Research Council of Finland
Finnish Diabetes Research Foundation
Suorsa Foundation, Gyllenberg Foundation
Deutsche Forschungsgemeinschaft
Diabetes Wellness Sweden
Karolinska Institutet
Research Council of Finland
Paulo Foundation
Novo Nordisk Foundation
Chair of Nutrition and Immunology at TUM