Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue. (15th May 2016)

• Record Type: Journal Article
• Authors: Kamble, Prasad G.; Pereira, Maria J.; Sidibeh, Cherno O.; Amini, Sam; Sundbom, Magnus; Börjesson, Joey Lau; Eriksson, Jan W.
• Is Part Of: Molecular and cellular endocrinology. Volume 427(2016)
• Page Start: 124
• Page End: 132
• Publication Date: 2016-05-15
• Subjects: Glucocorticoids -- Lipocalin 2 -- Human adipose tissue -- Type 2 diabetes -- Insulin resistance -- PPARγ; BCA Bicinchoninic acid protein -- BMI body mass index -- BSA Bovine serum albumin -- DMEM Dulbecco's modified eagle medium -- EDTA Ethylenediaminetetraacetic acid -- FBS Fetal bovine serum -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- GLUT1 Glucose transporter-1 -- GLUT4 Glucose transporter-4 -- IL-6 Interleukin-6 -- TNF α Tumor necrosis factor α -- KRH Krebs–Ringer media -- Lcn2 Lipocalin 2 -- PBS-T Phosphate Buffered Saline with Tween 20 -- PEST Penicillin-streptomycin -- PPARγ Peroxisome proliferator-activated receptor gamma -- rhLcn2 Recombinant human lipocalin 2 -- SVC Stromal vascular cells -- WST-1 Water-soluble tetrazolium-1; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.03.011
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males. Subcutaneous adipose tissue from both genders treated with recombinant human lipocalin 2 showed a reduction in protein levels of GLUT1 and GLUT4 and in glucose uptake in isolated adipocytes. In subcutaneous adipose tissue, lipocalin 2 increased IL-6 gene expression whereas expression of PPARγ and adiponectin was reduced. Our findings suggest that lipocalin 2 can contribute to insulin resistance in human adipose tissue. In pre-menopausal females, it may partly mediate adverse metabolic effects exerted by glucocorticoid excess. Highlights: This study demonstrates a role of lipocalin 2 in human adipose tissue metabolism. Dexamethasone induces lipocalin 2 gene expression in pre-menopausal females. Stromal vascular cells are major contributors of lipocalin 2 expression. Lipocalin 2 impairs basal and insulin-stimulated glucose uptake in adipocytes. Lipocalin 2 reduces PPARγ and adiponectin expression.