Prep1 deficiency improves metabolic response in white adipose tissue

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
Antonietta LiottiFrancesco Oriente

Abstract

Prep1 is a gene encoding for a homeodomain transcription factor which induces hepatic and muscular insulin resistance. In this study, we show that Prep1 hypomorphic heterozygous (Prep1i/+) mice, expressing low levels of protein, featured a 23% and a 25% reduction of total body lipid content and epididymal fat, respectively. The percentage of the small adipocytes (25-75 μm) was 30% higher in Prep1i/+ animals than in the WT, with a reciprocal difference in the large adipose cells (100-150 and >150 μm). Insulin-stimulated insulin receptor tyrosine and Akt serine phosphorylation markedly increased in Prep1i/+ mice, paralleled by 3-fold higher glucose uptake and a significant increase of proadipogenic genes such as C/EBPα, GLUT4, and FABP4. Moreover, T cells infiltration and TNF-α, IFNγ and leptin expression were reduced in adipose tissue from Prep1i/+ mice, while adiponectin levels were 2-fold higher. Furthermore, Prep1i/+ mature adipocytes released lower amounts of pro-inflammatory cytokines and higher amount of adiponectin compared to WT cells. Incubation of murine liver cell line (NMuLi) with conditioned media (CM) from mature adipocytes of Prep1i/+ mice improved glucose metabolism, while those from WT mice had no effect. Consis...Continue Reading

Citations

Oct 17, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ilaria CimminoFrancesco Oriente
Jul 14, 2018·Frontiers in Endocrinology·Francesco OrienteFrancesco Beguinot
Jul 28, 2019·International Journal of Molecular Sciences·Giorgia MaroniMaria Cristina Magli
Jul 31, 2021·Frontiers in Cell and Developmental Biology·Andreina BrunoElisabetta Pace

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