Lipocalin 2 regulates retinoic acid-induced activation of beige adipocytes
| Autor: | Hong Guo, Chengyu Liu, David A. Bernlohr, Yingjie Wu, Xiaoli Chen, Jessica A. Deis |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Retinoic acid Tretinoin White adipose tissue Article Mice 03 medical and health sciences chemistry.chemical_compound Endocrinology Lipocalin-2 Downregulation and upregulation Adipocyte Internal medicine Brown adipose tissue medicine Animals Adipocytes Beige Molecular Biology Cells Cultured Mice Mutant Strains Mitochondria 030104 developmental biology medicine.anatomical_structure Adipose Tissue chemistry Phosphorylation Signal transduction Thermogenesis Signal Transduction |
| Zdroj: | Journal of Molecular Endocrinology. 61:115-126 |
| ISSN: | 1479-6813 0952-5041 |
| DOI: | 10.1530/jme-18-0017 |
| Popis: | Lipocalin-2 (LCN2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for LCN2 in the recruitment and retinoic acid-induced activation of brown-like or ‘beige’ adipocytes. We found LCN2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived fromLcn2−/−mice.Lcn2−/−inguinal adipocytes have attenuated insulin-induced upregulation of thermogenic gene expression and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway activation. This is accompanied by a lower basal and maximal oxidative capacity inLcn2−/−inguinal adipocytes, indicating mitochondrial dysfunction. Recombinant Lcn2 was able to restore insulin-induced p38MAPK phosphorylation in both WT andLcn2−/−inguinal adipocytes. Rosiglitazone treatment during differentiation ofLcn2−/−adipocytes is able to recruit beige adipocytes at a normal level, however, further activation of beige adipocytes by insulin and RA is impaired in the absence of LCN2. Further, the synergistic effect of insulin and RA on UCP1 and PGC-1α expression is markedly reduced inLcn2−/−inguinal adipocytes. Most intriguingly, LCN2 and the retinoic acid receptor-alpha (RAR-α) are concurrently translocated to the plasma membrane of adipocytes in response to insulin, and this insulin-induced RAR-α translocation is absent in adipocytes deficient in LCN2. Our data suggest a novel LCN2-mediated pathway by which RA and insulin synergistically regulates activation of beige adipocytes via a non-genomic pathway of RA action. |
| Databáze: | OpenAIRE |
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