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

Denise E. Lackey, Felipe C.G. Reis, Roi Isaac, Rizaldy C. Zapata, Dalila El Ouarrat, Yun Sok Lee, Gautam Bandyopadhyay, Jachelle M. Ofrecio, Da Young Oh, Olivia Osborn

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number14779
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Obese Mice
Adipocytes
Insulin Resistance
Glucose
Obesity
Macrophages
Glucose Intolerance
Knockout Mice
Serine
Type 2 Diabetes Mellitus
Adipose Tissue
Homeostasis
Transcription Factors
Phosphorylation
Insulin
Inflammation
Gene Expression
Liver
Genes

ASJC Scopus subject areas

  • General

Cite this

Lackey, D. E., Reis, F. C. G., Isaac, R., Zapata, R. C., El Ouarrat, D., Lee, Y. S., ... Osborn, O. (2019). Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice. Scientific reports, 9(1), [14779]. https://doi.org/10.1038/s41598-019-51196-8

Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice. / Lackey, Denise E.; Reis, Felipe C.G.; Isaac, Roi; Zapata, Rizaldy C.; El Ouarrat, Dalila; Lee, Yun Sok; Bandyopadhyay, Gautam; Ofrecio, Jachelle M.; Oh, Da Young; Osborn, Olivia.

In: Scientific reports, Vol. 9, No. 1, 14779, 01.12.2019.

Research output: Contribution to journalArticle

Lackey, DE, Reis, FCG, Isaac, R, Zapata, RC, El Ouarrat, D, Lee, YS, Bandyopadhyay, G, Ofrecio, JM, Oh, DY & Osborn, O 2019, 'Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice', Scientific reports, vol. 9, no. 1, 14779. https://doi.org/10.1038/s41598-019-51196-8
Lackey DE, Reis FCG, Isaac R, Zapata RC, El Ouarrat D, Lee YS et al. Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice. Scientific reports. 2019 Dec 1;9(1). 14779. https://doi.org/10.1038/s41598-019-51196-8
Lackey, Denise E. ; Reis, Felipe C.G. ; Isaac, Roi ; Zapata, Rizaldy C. ; El Ouarrat, Dalila ; Lee, Yun Sok ; Bandyopadhyay, Gautam ; Ofrecio, Jachelle M. ; Oh, Da Young ; Osborn, Olivia. / Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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