title: Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1-deficient Mice.
abstract: Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis. This system is referred to as the gut-brain axis. Here we show that both brush cells and type II taste cells are eliminated in the gastrointestinal tract of transcription factor Skn-1 knockout (KO) mice. Despite unaltered food intake, Skn-1 KO mice have reduced body weight with lower body fat due to increased energy expenditure. In this model, 24-h urinary excretion of catecholamines was significantly elevated, accompanied by increased fatty acid β-oxidation and fuel dissipation in skeletal muscle and impaired insulin secretion driven by glucose. These results suggest the existence of brain-mediated energy homeostatic pathways originating from brush cells and type II taste cells in the gastrointestinal tract and ending in peripheral tissues, including the adrenal glands. The discovery of food-derived factors that regulate these cells may open new avenues the treatment of obesity and diabetes.
  
  
  BACKGROUND
  Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis along the gut-brain axis. We propose the concept that taste-receiving cells in the oral cavity and/or food-borne chemicals-receiving brush cells in the gut are involved in regulation of the body weight and adiposity via the brain. The discovery of food-derived factors that regulate these cells may open new avenues for the treatment of obesity and diabetes.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Ushiama
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Electronic address: ayishi@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishimaru
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Narukawa
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Yoshioka
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Chisayo
authors.initials: C
authors.lastname: Kozuka
authors.affiliation: Department of Bio-science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsunoda
authors.affiliation: Department of Bio-science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Osakabe
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Tomiko
authors.initials: T
authors.lastname: Asakura
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; Kanagawa Academy of Science and Technology, Takatsu-ku, Kawasaki-shi, Kanagawa, Japan. Electronic address: aka7308@mail.ecc.u-tokyo.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism* / Q000652:urine; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D018628:Gene Dosage; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D050810:Octamer Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002395:Catecholamines; D004272:DNA, Mitochondrial; D007328:Insulin; D050810:Octamer Transcription Factors; C084342:Pou2f3 protein, mouse
keywords: Brush cells; Catecholamine; Energy metabolism; Insulin