Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue

• Published in: Molecular and cellular endocrinology Vol. 427; pp. 124 - 132
• Main Authors: Kamble, Prasad G., Pereira, Maria J., Sidibeh, Cherno O., Amini, Sam, Sundbom, Magnus, Börjesson, Joey Lau, Eriksson, Jan W.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 15-05-2016
• Subjects: Adiponectin - genetics; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose tissues; Adult; Aged; Cellular; Dexamethasone - pharmacology; Female; Females; Gene expression; Glucocorticoids; Glucocorticoids - chemical synthesis; Glucocorticoids - physiology; Glucose; Glucose - metabolism; Human; Human adipose tissue; Humans; Insulin; Insulin Resistance; Lipocalin 2; Lipocalin-2 - metabolism; Lipocalin-2 - physiology; Male; Middle Aged; PPAR gamma; PPAR gamma - metabolism; PPARγ; Recombinant Proteins - pharmacology; Subcutaneous Fat - drug effects; Subcutaneous Fat - metabolism; Type 2 diabetes; Up-Regulation; Young Adult; Lipocalin 2; Type 2 diabetes; KRH; BCA; GLUT1; SVC; Glucocorticoids; EDTA; WST-1; PPARγ; IL-6; PBS-T; BSA; DMEM; PEST; FBS; rhLcn2; Insulin resistance; TNF α; GLUT4; GAPDH; Human adipose tissue; BMI; Lcn2
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2016.03.011

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.
•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.