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Le Duc, D.* ; Lin, C.C.* ; Popkova, Y.* ; Yang, Z.* ; Akhil, V.* ; Çakir, M.V.* ; Grunewald, S.* ; Simon, J.C.* ; Dietz, A.* ; Dannenberger, D.* ; Garten, A.* ; Lemke, J.R.* ; Schiller, J.* ; Blüher, M. ; Nono Nankam, P.A.* ; Rolle-Kampczyk, U.* ; von Bergen, M.* ; Kelso, J.* ; Schöneberg, T.*

Reduced lipolysis in lipoma phenocopies lipid accumulation in obesity.

Int. J. Obes. 45, 565–576 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Background: Elucidation of lipid metabolism and accumulation mechanisms is of paramount importance to understanding obesity and unveiling therapeutic targets. In vitro cell models have been extensively used for these purposes, yet, they do not entirely reflect the in vivo setup. Conventional lipomas, characterized by the presence of mature adipocytes and increased adipogenesis, could overcome the drawbacks of cell cultures. Also, they have the unique advantage of easily accessible matched controls in the form of subcutaneous adipose tissue (SAT) from the same individual. We aimed to determine whether lipomas are a good model to understand lipid accumulation. Methods: We histologically compared lipomas and control SAT, followed by assessment of the lipidome using high-resolution 1H NMR spectroscopy and ESI-IT mass spectrometry. RNA-sequencing was used to obtain the transcriptome of lipomas and the matched SAT. Results: We found a significant increase of small-size (maximal axis < 70 µm) and very big (maximal axis > 150 µm) adipocytes within lipomas. This suggests both enhanced adipocyte proliferation and increased lipid accumulation. We further show that there is no significant change in the lipid composition compared to matched SAT. To better delineate the pathophysiology of lipid accumulation, we considered two groups with different genetic backgrounds: (1) lipomas with HMGA2 fusions and (2) without gene fusions. To reduce the search space for genes that are relevant for lipid pathophysiology, we focused on the overlapping differentially expressed (DE) genes between the two groups. Gene Ontology analysis revealed that DE genes are enriched in pathways related to lipid accumulation. Conclusions: We show that the common shared lipid accumulation mechanism in lipoma is a reduction in lipolysis, with most gene dysregulations leading to a reduced cAMP in the adipocyte. Superficial lipomas could thus be used as a model for lipid accumulation through altered lipolysis as found in obese patients.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Pulmonary Chondroid Hamartomas; Adipose-tissue; Protein Expression; Fusion Transcript; Gene-expression; Weight-loss; Hmga2; Identification; Adipogenesis; Networks
ISSN (print) / ISBN 0307-0565
e-ISSN 1476-5497
Quellenangaben Volume: 45, Issue: , Pages: 565–576 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Deutsche Forschungsgemeinschaft