title: Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation.
abstract: Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet -fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosis.
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Korea.
authors.forename: No-Joon
authors.initials: NJ
authors.lastname: Song
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Ui Jeong
authors.initials: UJ
authors.lastname: Yun
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences &Biotechnology, BK21-PLUS program, Korea University, 136-713 Seoul Korea.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Korea.
authors.forename: Cho-Rong
authors.initials: CR
authors.lastname: Seo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.|Department of Internal Medicine, Graduate School of Medicine, Gachon University of Medicine and Science.
authors.forename: A-Ryeong
authors.initials: AR
authors.lastname: Gwon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Sang-Ha
authors.initials: SH
authors.lastname: Baik
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Gahee
authors.initials: G
authors.lastname: Bahn
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Korea.
authors.forename: Suji
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Korea.
authors.forename: So-Mi
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Park
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Baek
authors.affiliation: School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology.
authors.forename: Tae Joo
authors.initials: TJ
authors.lastname: Park
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Korea.
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, Gachon University of Medicine and Science.
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences &Biotechnology, BK21-PLUS program, Korea University, 136-713 Seoul Korea.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Korea.
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004032:Diet / Q000009:adverse effects; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000172:deficiency* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005227:Fatty Acids; D051881:Receptor, Notch1