ArticleMolecular and cellular biology2015
Uncoupling lipid metabolism from inflammation through fatty acid binding protein-dependent expression of UCP2.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 104 citations in OpenAlex.
- Serum FABP4 concentrations decrease after Roux-en-Y gastric bypass but not after intensive medical management.Surgery · 2019Trial
- Exploring the significance of fatty acid-binding protein 4 levels as a biomarker for autism spectrum disorder: a cross-sectional study.BMC psychiatry · 2026Article
- Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells.Aging cell · 2025Article
- Multiple Roles of Palmitic Acid in Cardiovascular Diseases.Journal of inflammation research · 2025Review
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- Article
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- The Molecular Mechanism of FABP4 Inhibition Effects of GAS and 4-HBA inJournal of analytical methods in chemistry · 2024Article
- Fatty Acid-Binding Protein 4 is Essential for the Inflammatory and Metabolic Response of Microglia to Lipopolysaccharide.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- The Multifunctional Family of Mammalian Fatty Acid-Binding Proteins.Annual review of nutrition · 2023Review
- RNAseq Analysis of FABP4 Knockout Mouse Hippocampal Transcriptome Suggests a Role for WNT/β-Catenin in Preventing Obesity-Induced Cognitive Impairment.International journal of molecular sciences · 2023Article
- Cellular crosstalk of macrophages and therapeutic implications in non-small cell lung cancer revealed by integrative inference of single-cell transcriptomics.Frontiers in pharmacology · 2023Article
- FABP4-mediated lipid droplet formation in Streptococcus uberis-infected macrophages supports host defence.Veterinary research · 2022Article
- Thiosulfate-Cyanide Sulfurtransferase a Mitochondrial Essential Enzyme: From Cell Metabolism to the Biotechnological Applications.International journal of molecular sciences · 2022Review
- Spexin modulates molecular thermogenic profile of adipose tissue and thermoregulatory behaviors in female C57BL/6 mice.Hormones and behavior · 2022Article
- Microglial FABP4-UCP2 Axis Modulates Neuroinflammation and Cognitive Decline in Obese Mice.International journal of molecular sciences · 2022Article
- Fatty acid-binding protein 4 is a therapeutic target for septic acute kidney injury by regulating inflammatory response and cell apoptosis.Cell death & disease · 2022Article
- Single-nucleotide polymorphisms as important risk factors of diabetes among Middle East population.Human genomics · 2022Review
- Fatty acid binding protein 4 regulates pancreatic cancer cell proliferation via activation of nuclear factor E2-related factor 2.Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery · 2022Article
- Inflammasome Activation and Pyroptosis via a Lipid-regulated SIRT1-p53-ASC Axis in Macrophages From Male Mice and Humans.Endocrinology · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic inflammation in obese adipose tissue is linked to endoplasmic reticulum (ER) stress and systemic insulin resistance. Targeted deletion of the murine fatty acid binding protein (FABP4/aP2) uncouples obesity from inflammation although the mechanism underlying this finding has remained enigmatic. Here, we show that inhibition or deletion of FABP4/aP2 in macrophages results in increased intracellular free fatty acids (FFAs) and elevated expression of uncoupling protein 2 (UCP2) without concomitant increases in UCP1 or UCP3. Silencing of UCP2 mRNA in FABP4/aP2-deficient macrophages negated the protective effect of FABP loss and increased ER stress in response to palmitate or lipopolysaccharide (LPS). Pharmacologic inhibition of FABP4/aP2 with the FABP inhibitor HTS01037 also upregulated UCP2 and reduced expression of BiP, CHOP, and XBP-1s. Expression of native FABP4/aP2 (but not the non-fatty acid binding mutant R126Q) into FABP4/aP2 null cells reduced UCP2 expression, suggesting that the FABP-FFA equilibrium controls UCP2 expression. FABP4/aP2-deficient macrophages are resistant to LPS-induced mitochondrial dysfunction and exhibit decreased mitochondrial protein carbonylation and UCP2-dependent reduction in intracellular reactive oxygen species. These data demonstrate that FABP4/aP2 directly regulates intracellular FFA levels and indirectly controls macrophage inflammation and ER stress by regulating the expression of UCP2.
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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.