Related Experiment Video

Updated: Oct 6, 2025

Assessing Hepatic Metabolic Changes During Progressive Colonization of Germ-free Mouse by 1H NMR Spectroscopy
07:54

Assessing Hepatic Metabolic Changes During Progressive Colonization of Germ-free Mouse by 1H NMR Spectroscopy

Published on: December 15, 2011

13.2K

Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver

Jian Jin1,2, Banrida Wahlang3,4, Monika Thapa5

  • 1Department of Pharmacology & Toxicology, the University of Louisville School of Medicine, Louisville, KY 40202, USA.

Acta Pharmaceutica Sinica. B
|January 13, 2022
PubMed

Insights

The aryl hydrocarbon receptor (AHR) plays a key role in regulating liver metabolism, impacting lipids, xenobiotics, and endocrine function. Genetic ablation of AHR significantly altered metabolic health and liver characteristics, highlighting its importance in liver disease.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Metabolomics

Background:

  • Dioxin-like molecules are linked to endocrine disruption and liver disease.
  • The aryl hydrocarbon receptor (AHR) is a key mediator of responses to these molecules.
  • Understanding AHR's role in liver health and disease is crucial.

Purpose of the Study:

  • To investigate the impact of AHR activation and genetic ablation on liver metabolism and proteome.
  • To elucidate the specific roles of AHR in regulating liver function and endocrine responses.

Main Methods:

  • Metabolic phenotyping and liver proteomics in wild-type (WT) and AHR-deficient (Ahr-/-) mice.
  • Exposure to a dioxin-like compound, PCB126, or vehicle control.
  • Analysis of gene expression, body composition, glucose tolerance, liver histology, and blood lipids.

Main Results:

  • AHR deficiency led to increased adiposity, decreased glucose tolerance, smaller livers with steatosis, and paradoxically lower blood lipids.
  • PCB126 exposure increased hepatic triglycerides in Ahr-/- mice.
  • AHR primarily regulated liver metabolism (lipids, xenobiotics) and bioenergetics, but also impacted endocrine functions and protein production.

Conclusions:

  • AHR is a critical regulator of liver metabolic and endocrine homeostasis.
  • AHR deficiency profoundly impacts liver health and metabolic status.
  • Further research into AHR's role is warranted for understanding and treating liver metabolic diseases.
Keywords:
AHRAHR, aryl hydrocarbon receptorALT, alanine transaminaseANOVA, analysis of varianceAST, aspartate transaminaseAUC, area under the curveCAR, constitutive androstane receptorCD36, cluster of differentiation 36CYP, cytochrome P450EPF, enrichment by protein functionEndocrine disruptionEnvironmental liver diseaseFDR, false discovery rateFGF21, fibroblast growth factor 21GCR, glucocorticoid receptorGO, gene ontologyH&E, hematoxylin-eosinHDL, high-density lipoproteinHFD, high fat dietIGF1, insulin-like growth factor 1IL-6, interleukin 6IPF, interaction by protein functionLDL, low-density lipoproteinMCP-1, monocyte chemoattractant protein-1MUP, major urinary proteinNAFLD, non-alcoholic fatty liver diseaseNFKBIA, nuclear factor kappa-inhibitor alphaNonalcoholic fatty liver diseasePAI-1, plasminogen activator inhibitor-1PCB, polychlorinated biphenylPCB126PLIN2, perilipin-2PNPLA3, patatin-like phospholipase domain-containing protein 3PPARα, peroxisome proliferator-activated receptor alphaPXR, pregnane-xenobiotic receptorPerilipin-2PheromonesSGK1, serum/glucocorticoid regulated kinaseTAFLD, toxicant-associated fatty liver diseaseTASH, toxicant-associated steatohepatitisTAT, tyrosine aminotransferaseTMT, tandem mass tagVLDL, very low-density lipoproteinWT, wild typeZFP125, zinc finger protein 125miR, microRNAnHDLc, non-HDL cholesterol

More Related Videos

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.2K
Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes12:11

Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes

Published on: August 27, 2015

20.5K

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.8K
Proteomics01:33

Proteomics

A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
8.4K