Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice.

Autor: Lackey DE; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Reis FCG; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Isaac R; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Zapata RC; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., El Ouarrat D; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Lee YS; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Bandyopadhyay G; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Ofrecio JM; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA., Oh DY; Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, USA., Osborn O; Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. oosborn@ucsd.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Oct 14; Vol. 9 (1), pp. 14779. Date of Electronic Publication: 2019 Oct 14.
DOI: 10.1038/s41598-019-51196-8
Abstrakt: Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.
Databáze: MEDLINE
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