ArticleInternational journal of obesity (2005)2019
IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity.
Article in International journal of obesity (2005), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 40 citations in OpenAlex.
- Identification of a specific set of genes predicting obesity before phenotype appearance.iScience · 2025Article
- IRX5 Promoted SREBP1-Mediated de Novo Fatty Acid Synthesis via HMGN4 in Hepatocellular Carcinoma.Journal of cellular and molecular medicine · 2025Article
- Long non-coding RNAs mediate fish gene expression in response to ocean acidification.Evolutionary applications · 2024Article
- Identification of Potentially Novel Molecular Targets of Endometrial Cancer Using a Non-Biased Proteomic Approach.Cancers · 2023Article
- Technologies, strategies, and cautions when deconvoluting genome-wide association signals: FTO in focus.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023Review
- Food preferences after bariatric surgery: a review update.Internal and emergency medicine · 2023Review
- The Characterization and Differential Analysis of mAnimals : an open access journal from MDPI · 2023Article
- Corrigendum: Human abdominal subcutaneous-derived active beige adipocytes carryingFrontiers in cell and developmental biology · 2023Article
- Human abdominal subcutaneous-derived active beige adipocytes carryingFrontiers in cell and developmental biology · 2023Article
- Recruitment of CTCF to anProceedings of the National Academy of Sciences of the United States of America · 2022Article
- MRI adipose tissue segmentation and quantification in R (RAdipoSeg).Diabetology & metabolic syndrome · 2022Article
- IRX5 promotes adipogenesis of hMSCs by repressing glycolysis.Cell death discovery · 2022Article
- Mitochondrial regulation and white adipose tissue homeostasis.Trends in cell biology · 2022Review
- Molecular Typing Based on Oxidative Stress Genes and Establishment of Prognostic Characteristics of 7 Genes in Lung Adenocarcinoma.Oxidative medicine and cellular longevity · 2022Article
- Article
- Whole genome transcriptome analysis of the stomach resected in human vertical sleeve gastrectomy: cutting more than calories.Physiological genomics · 2021Article
- Review
- Identification of Key Pathways and Genes in Obesity Using Bioinformatics Analysis and Molecular Docking Studies.Frontiers in endocrinology · 2021Article
- Article
- Dysregulation of Amyloid Precursor Protein Impairs Adipose Tissue Mitochondrial Function and Promotes Obesity.Nature metabolism · 2019Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveA causal obesity risk variant in the FTO locus was recently shown to inhibit adipocyte thermogenesis via increased adipose expression of the homeobox transcription factors IRX3 and IRX5. However, causal effects of IRX5 on fat storage remain to be shown in vivo, and discovery of downstream mediators may open new therapeutic avenues.
methods17 WT and 13 Irx5 knockout (KO) mice were fed low-fat control (Ctr) or high-fat (HF) diet for 10 weeks. Body weight, energy intake and fat mass were measured. Irx5-dependent gene expression was explored by transcriptome analysis of epididymal white adipose tissue (eWAT), confirmatory obesity-dependent expression in human adipocytes in vivo, and in vitro knock-down, overexpression and transcriptional activation assays.
resultsIrx5 knock-out mice weighed less, had diminished fat mass, and were protected from diet-induced fat accumulation. Key adipose mitochondrial genes Pparγ coactivator 1-alpha (Pgc-1α) and uncoupling protein 1 (Ucp1) were upregulated, and a gene network centered on amyloid precursor protein (App) was downregulated in adipose tissue of knock-out mice and in isolated mouse adipocytes with stable Irx5 knock-down. An APP-centered network was also enriched in isolated adipocytes from obese compared to lean humans. IRX5 overexpression increased APP promoter activity and both IRX5 and APP inhibited transactivation of PGC-1α and UCP1. Knock-down of Irx5 or App increased mitochondrial respiration in adipocytes.
conclusionIrx5-KO mice were protected from obesity and this can partially be attributed to reduced adipose App and improved mitochondrial respiration. This novel Irx5-App pathway in adipose tissue is a possible therapeutic entry point against obesity.
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