Decreased adipocyte-specific Olfactomedin 2 in obesity is a critical driver of defective fat cell cycle and adipose tissue accretion
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ABSTRACT: Olfactomedin 2 (OLFM2) is a central player in development that also appears to be a critical mediator for energy handling. Here we report that in adipose tissue, expression of OLFM2 is opposite to obesity, being increased upon weight loss. Concurrently, we show steadily increased OLFM2 during adipogenesis, with expression levels reaching its zenith in terminally differentiated adipocytes. Notably, we demonstrate that the loss of this specific olfactomedin domain-containing protein in fat cell progenitors dampens adipogenesis, while the adipogenic conversion is bolstered in engineered 3T3-L1 cells with increased OLFM2. Our seminal findings also bound dwindled expressions of adipocyte-specific OLFM2 to the inflammatory state in the context of obesity, mainly characterized by the influence of macrophage-derived cytokines. Then, we show that the loss of OLFM2 in human adipocytes displays the transient downregulation of genes related to cell cycle, also coupled to deranged energy storage. Next, we transitioned our results to mice models in which whole-body knockout and transcriptionally regulated adipose-specific Olfm2 compel a cluster of molecular changes tightly related to impaired cell cycle (in both) and fat mass accretion (in the later). Current findings unveil the previously unknown expression of OLFM2 in adipocytes and the control of cellular mechanisms related to the obese phenotype exercised by this scaffold protein in adipose tissues.
ORGANISM(S): Mus musculus
PROVIDER: GSE214900 | GEO | 2023/12/31
REPOSITORIES: GEO
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