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Kynurenine‐Induced Aryl Hydrocarbon Receptor Signaling in Mice Causes Body Mass Gain, Liver Steatosis, and Hyperglycemia
Author(s) -
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.
Publication year - 2021
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.23065
Subject(s) - aryl hydrocarbon receptor , endocrinology , medicine , kynurenine , steatosis , metabolite , fatty liver , chemistry , tryptophan , biochemistry , gene , disease , amino acid , transcription factor
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.