title: Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice.
abstract: 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.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Sungwook
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Taeyun A
authors.initials: TA
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Song
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea. Electronic address: bypark@yonsei.ac.kr.
authors.forename: Boyoun
authors.initials: B
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D059305:Diet, High-Fat; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation; D012322:RNA Precursors / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D012322:RNA Precursors; D012333:RNA, Messenger; C578077:Tardbp protein, mouse
keywords: High-fat diet (HFD) mice; Interleukin-6; Obesity; Pre-mRNA processing; Tat-activating regulatory DNA-binding protein-43 (TDP-43)