ArticleJCI insight2021
ANT2 drives proinflammatory macrophage activation in obesity.
Article in JCI insight, 2021. 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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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Interferon-alpha selectively signals mitochondrial pore opening to allow mitochondrial RNA release in systemic lupus erythematosus: pathophysiological implications.Cell communication and signaling : CCS · 2026Article
- The organelle oxidative-inflammatory network in polycystic ovary syndrome: from subcellular intercellular cascades to systemic comorbidities.Frontiers in immunology · 2026Review
- Targeting macrophage metabolism: mechanisms, cellular crosstalk and implications in obesity-associated metabolic diseases.Frontiers in immunology · 2026Review
- Immunometabolism in obesity: Understanding the beneficial and detrimental roles of inflammation.PLoS biology · 2026Article
- ANT1 Deficiency Impairs Macrophage Metabolism and Migration, Protecting Against Emphysema in Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2025Article
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- Mitochondrial uncoupling, energy substrate utilization, and brown adipose tissue as therapeutic targets in cancer.npj metabolic health and disease · 2025Review
- BNIP3-mediated mitophagy in macrophages regulates obesity-induced adipose tissue metaflammation.Autophagy · 2025Article
- Deletion of EP3 prostaglandin receptor in murine macrophages aggravates diet-induced obesity by suppressing SPARC.The EMBO journal · 2025Article
- Mild Mitochondrial Uncoupling for True Ectopic Lipid Disposal.International journal of molecular sciences · 2025Review
- Flavonoids of Mao Jian Green Tea Ameliorate Glycemic Metabolism in Type-2-Diabetic Rats via AMPK Signaling Pathways and Gut Microbiota Regulation.Foods (Basel, Switzerland) · 2025Article
- Metabolic reprogramming driven by Ant2 deficiency augments T Cell function and anti-tumor immunity in mice.Nature communications · 2025Article
- Diverse Functions of Macrophages in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease: Bridging Inflammation and Metabolism.Immune network · 2025Review
- A genome-wide association analysis reveals new pathogenic pathways in gout.Nature genetics · 2024Article
- Dynamic Roles and Expanding Diversity of Adipose Tissue Macrophages in Obesity.Journal of obesity & metabolic syndrome · 2024Review
- HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.Science translational medicine · 2024Article
- HOXC11-mediated regulation of mitochondrial function modulates chemoresistance in colorectal cancer.BMC cancer · 2024Article
- Unraveling the complex roles of macrophages in obese adipose tissue: an overview.Frontiers of medicine · 2024Review
- Obese visceral fat tissue inflammation: from protective to detrimental?BMC medicine · 2022Review
- Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Macrophage proinflammatory activation is an important etiologic component of the development of insulin resistance and metabolic dysfunction in obesity. However, the underlying mechanisms are not clearly understood. Here, we demonstrate that a mitochondrial inner membrane protein, adenine nucleotide translocase 2 (ANT2), mediates proinflammatory activation of adipose tissue macrophages (ATMs) in obesity. Ant2 expression was increased in ATMs of obese mice compared with lean mice. Myeloid-specific ANT2-knockout (ANT2-MKO) mice showed decreased adipose tissue inflammation and improved insulin sensitivity and glucose tolerance in HFD/obesity. At the molecular level, we found that ANT2 mediates free fatty acid-induced mitochondrial permeability transition, leading to increased mitochondrial reactive oxygen species production and damage. In turn, this increased HIF-1α expression and NF-κB activation, leading to proinflammatory macrophage activation. Our results provide a previously unknown mechanism for how obesity induces proinflammatory activation of macrophages with propagation of low-grade chronic inflammation (metaflammation).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.