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Kynurenine-Induced Aryl Hydrocarbon Receptor Signaling in Mice Causes Body Mass Gain, Liver Steatosis, and Hyperglycemia.
Rojas, Itzel Y; Moyer, Benjamin J; Ringelberg, Carol S; Wilkins, Owen M; Pooler, Darcy B; Ness, Dylan B; Coker, Shodeinde; Tosteson, Tor D; Lewis, Lionel D; Chamberlin, Mary D; Tomlinson, Craig R.
Afiliação
  • Rojas IY; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Moyer BJ; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Ringelberg CS; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Wilkins OM; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Pooler DB; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Ness DB; Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Coker S; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Tosteson TD; Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Lewis LD; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Chamberlin MD; Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  • Tomlinson CR; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Obesity (Silver Spring) ; 29(2): 337-349, 2021 02.
Article em En | MEDLINE | ID: mdl-33491319
OBJECTIVE: The aryl hydrocarbon receptor (AHR) plays a key role in obesity. In vitro studies revealed that the tryptophan metabolite kynurenine (Kyn) activates AHR signaling in cultured hepatocytes. The objective of this study was to determine whether Kyn activated the AHR in mice to induce obesity. METHODS: Mice were fed a low-fat diet and the same diet supplemented with Kyn. Body mass, liver status, and the expression of identified relevant genes were determined. RESULTS: Kyn caused mice to gain significant body mass, develop fatty liver and hyperglycemia, and increase expression levels of cytochrome P450 1B1 and stearoyl-CoA desaturase 1. The hyperglycemia was accompanied with decreased insulin levels, which may have been due to the repression of genes involved in insulin secretion. Kyn plasma concentrations and BMI were measured in female patients, and a significant association was observed between Kyn and age in patients with obesity but not in patients who were lean. CONCLUSIONS: Results show that (1) Kyn or a metabolite thereof is a ligand responsible for inducing AHR-based obesity, fatty liver, and hyperglycemia in mice; (2) plasma Kyn levels increase with age in women with obesity but not in lean women; and (3) an activated AHR is necessary but not sufficient to attain obesity, a status that also requires fat in the diet.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aumento de Peso / Receptores de Hidrocarboneto Arílico / Fígado Gorduroso / Hiperglicemia / Cinurenina Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aumento de Peso / Receptores de Hidrocarboneto Arílico / Fígado Gorduroso / Hiperglicemia / Cinurenina Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article