Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice
| Autor: | Taeyun A. Lee, Taesun Park, Boyoun Park, Su Jin Song, Sungwook Lee |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Biophysics Hyperphosphorylation Adipose tissue Enzyme-Linked Immunosorbent Assay Tat-activating regulatory DNA-binding protein-43 (TDP-43) Disease Biology Diet High-Fat Real-Time Polymerase Chain Reaction Biochemistry Mice Structural Biology In vivo 3T3-L1 Cells Internal medicine mental disorders RNA Precursors Genetics medicine Animals Humans Obesity RNA Messenger Phosphorylation RNA Processing Post-Transcriptional Interleukin 6 Molecular Biology DNA Primers Messenger RNA Base Sequence Interleukin-6 nutritional and metabolic diseases Cell Biology medicine.disease nervous system diseases DNA-Binding Proteins HEK293 Cells Endocrinology Pre-mRNA processing High-fat diet (HFD) mice Immunology biology.protein Homeostasis |
| Zdroj: | FEBS Letters. 589:1825-1831 |
| ISSN: | 0014-5793 |
| Popis: | Inclusion of Tat-activating regulatory DNA-binding protein-43 (TDP-43) due to hyperphosphorylation or hyperubiquitination is a cause of neurodegenerative disease. Cellular TDP-43 expression is tightly controlled through a negative feedback loop involving its mRNA. Recently, we reported that the TDP-43-mediated sub-nuclear body is an essential site of interleukin-6 (IL-6) pre-mRNA processing. Here we show that mice fed on a high-fat diet exhibit increased TDP-43 expression in the liver and adipose tissue with a prominent increase in IL-6. TDP-43 depletion in vivo reduces IL-6 production in the liver. Overexpression or depletion of TDP-43 in pre-adipose and adipose cells causes reciprocal alteration of IL-6 expression and RNA processing. Our findings provide evidence for a link between homeostasis of TDP-43 expression and the risk of developing obesity. |
| Databáze: | OpenAIRE |
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