MassIVE MSV000098300

Partial Public PXD065388

Defective Olfactomedin-2 connects adipocyte dysfunction to obesity

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Description

Olfactomedin-2 (OLFM2) is a pleiotropic glycoprotein emerging as a regulator of energy homeostasis. We here show the expression of OLFM2 to be adipocyte-specific and inversely associated with obesity. OLFM2 levels increase during adipocyte differentiation and are suppressed in inflamed adipocytes. Functionally, OLFM2 deficiency impairs adipogenesis, while its over-production enhances the transformation of fat cell progenitors. Loss and gain of function experiments revealed that OLFM2 modulates key metabolic and structural pathways, including PPAR signaling, citrate cycle, fatty acid degradation, axon guidance and focal adhesion. On the molecular level, OLFM2 deficiency in adipocytes predominantly downregulates genes involved in cell cycle. Extending these findings in vivo, both whole-body Olfm2 knockout and adipose-specific Olfm2 depletion resulted in impaired adipose cell cycle gene expression, with the latter also displaying fat mass accretion and metabolic dysfunction. Collectively, our results underscore a critical role for OLFM2 in adipocyte biology, and support a causative link between reduced adipose OLFM2 and the pathophysiology of obesity. [doi:10.25345/C5Z31P19P] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: dia ; mouse ; TimsTof Ultra ; Dia-NN ; uPAC ; autonomics ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Francisco J. Ortega, Ph.D., Institut d'Investigacio Biomedica de Girona (IDIBGI), Spain
Submitting User: Wszymanski

Publications

Lluch A, Latorre J, Espadas I, Oliveras-Cañellas N, Moreno-Navarrete JM, Caballano-Infantes E, Sarker G, Malvido NF, Garrido-Gil P, Labandeira-García JL, Nakaya N, Mora S, Chicano E, López-Alcalá J, Malagón MM, Martín-Montalvo A, Zhang B, Zhou Y, Domingos AI, López M, Pörschke J, Gómez-Serrano M, Szymanski W, Graumann J, Tomarev SI, González-García I, Fernández-Real JM, Ortega FJ.
Defective Olfactomedin-2 connects adipocyte dysfunction to obesity.
Nat Commun. 2025 Aug 4;16(1):7154. Epub 2025 Aug 4.

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