Disruption of Lipid Raft Function Increases Expression and Secretion of Monocyte Chemoattractant Protein-1 in 3T3-L1 Adipocytes
| Autor: | Chia-Shan Yeh, Yu-Tzu Chang, Juu-Chin Lu, Yu-Ting Chiang, Yu-Chun Lin, Tzu-Yu Chen, Chia-Yun Lu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Physiology Cell Membranes lcsh:Medicine Biochemistry Mice chemistry.chemical_compound 0302 clinical medicine Cell Signaling Animal Cells Adipocyte Adipocytes Medicine and Health Sciences Enzyme-Linked Immunoassays lcsh:Science Lipid raft Chemokine CCL2 Connective Tissue Cells Multidisciplinary beta-Cyclodextrins NF-kappa B Cell Differentiation Lipids Cell biology Cholesterol Physiological Parameters Connective Tissue Lipid Signaling lipids (amino acids peptides and proteins) Cellular Types Anatomy Cellular Structures and Organelles Signal transduction Research Article Signal Transduction 030209 endocrinology & metabolism Research and Analysis Methods Filipin Proinflammatory cytokine 03 medical and health sciences Membrane Microdomains 3T3-L1 Cells Animals Secretion Obesity Immunoassays Body Weight lcsh:R Biology and Life Sciences 3T3-L1 Cell Biology Biological Tissue 030104 developmental biology Gene Expression Regulation chemistry Immunologic Techniques lcsh:Q Physiological Processes |
| Zdroj: | PLoS ONE, Vol 11, Iss 12, p e0169005 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0169005 |
| Popis: | The adipocyte is unique in its capacity to store lipids. In addition to triglycerides, the adipocyte stores a significant amount of cholesterol. Moreover, obese adipocytes are characterized by a redistribution of cholesterol with depleted cholesterol in the plasma membrane, suggesting that cholesterol perturbation may play a role in adipocyte dysfunction. We used methyl-β-cyclodextrin (MβCD), a molecule with high affinity for cholesterol, to rapidly deplete cholesterol level in differentiated 3T3-L1 adipocytes. We tested whether this perturbation altered adipocyte secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that is elevated in obesity and is linked to obesity-associated chronic diseases. Depletion of cholesterol by MβCD increased MCP-1 secretion as well as the mRNA and protein levels, suggesting perturbation at biosynthesis and secretion. Pharmacological inhibition revealed that NF-κB, but not MEK, p38 and JNK, was involved in MβCD-stimulated MCP-1 biosynthesis and secretion in adipocytes. Finally, another cholesterol-binding drug, filipin, also induced MCP-1 secretion without altering membrane cholesterol level. Interestingly, both MβCD and filipin disturbed the integrity of lipid rafts, the membrane microdomains enriched in cholesterol. Thus, the depletion of membrane cholesterol in obese adipocytes may result in dysfunction of lipid rafts, leading to the elevation of proinflammatory signaling and MCP-1 secretion in adipocytes. |
| Databáze: | OpenAIRE |
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