Adiponectin Enhances Human Keratinocyte Lipid Synthesis via SIRT1 and Nuclear Hormone Receptor Signaling
Autor: | H. Seo, Myungjin Park, Seung-Phil Hong, Myung Hwa Kim, Kyungho Park, Byung Cheol Park, Seong Jun Seo, Chang Deok Kim, Kyong-Oh Shin |
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Rok vydání: | 2019 |
Předmět: |
Keratinocytes
0301 basic medicine Ceramide Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Dermatology Real-Time Polymerase Chain Reaction Biochemistry Gas Chromatography-Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sirtuin 1 Lipid biosynthesis Animals Humans RNA Small Interfering Liver X receptor Receptor Molecular Biology Cells Cultured chemistry.chemical_classification Adiponectin receptor 1 Adiponectin Chemistry Lipogenesis Lipid metabolism Cell Biology Cell biology 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) hormones hormone substitutes and hormone antagonists Signal Transduction |
Zdroj: | Journal of Investigative Dermatology. 139:573-582 |
ISSN: | 0022-202X |
DOI: | 10.1016/j.jid.2018.08.032 |
Popis: | Adiponectin is known to have beneficial effects on lipid and insulin metabolism, wound healing, and cellular senescence, but its effect on skin barrier formation remains unknown. We investigated the effects of adiponectin on keratinocyte lipid synthesis with respect to skin barrier function. Lipid staining revealed an adiponectin-mediated increase in keratinocyte intracellular and reconstructed epidermal lipid content. Moreover, significant increases in the levels of ceramide and its downstream metabolites (sphingosine and sphingosine-1-phosphate) following adiponectin stimulation were detected using liquid chromatography-mass spectrometry. Expression levels of keratinocyte differentiation markers were also increased. Adiponectin also increased expression of lipid biosynthesis enzymes (fatty acid synthase, HMG-CoA reductase, and serine palmitoyltransferase), nuclear hormone receptors (peroxisome proliferator-activated receptors and liver X receptors), and the adiponectin signal molecule SIRT1. Suppression of SIRT1, liver X receptor-α, or peroxisome proliferator-activated receptor-α downregulated the expression of lipid synthetic enzymes, decreasing lipid content. Inhibition of adiponectin receptors decreased expression of nuclear hormone receptors, SIRT1, lipid-synthesizing enzymes, and sphingolipids. Thus, activation of adiponectin signaling increases the expression of transcription factors, including SIRT1, liver X receptor-α, and peroxisome proliferator-activated receptor-α, enhancing lipid synthesis and keratinocyte cell differentiation and possibly aiding in the maintenance of skin barrier homeostasis. |
Databáze: | OpenAIRE |
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