ArticleThe Journal of clinical investigation2017
Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 84 citations in OpenAlex.
- Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages.The Journal of clinical investigation · 2019Trial
- The arginine-phenylalanine-amide neuropeptide receptor family: Physiological effects, drug development, and structural insights.Neural regeneration research · 2026Article
- Targeting perivascular adipose tissue in vascular aging: innovative translational strategies for disease prevention and monitoring.Apoptosis : an international journal on programmed cell death · 2026Review
- Recessive Effect ofAnimals : an open access journal from MDPI · 2025Article
- Alkylglycerol monooxygenase represses prostanoid biosynthesis in a sex-dependent manner.Cell & bioscience · 2025Article
- Serum Neuropeptide FFR2 is increased in pregnant women with pre-eclampsia and associated with pregnancy outcomes.Pakistan journal of medical sciences · 2025Article
- Endurance training promotes the browning of WAT by enhancing the NPFF pathway in the hypothalamus in rats with type 2 diabetes.Iranian journal of basic medical sciences · 2025Article
- Progression in the In Vitro Macrophage Expansion.Journal of immunology research · 2025Review
- An Overview on Renal and Central Regulation of Blood Pressure by Neuropeptide FF and Its Receptors.International journal of molecular sciences · 2024Review
- Article
- Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure.Scientific reports · 2024Article
- A GPCR-neuropeptide axis dampens hyperactive neutrophils by promoting an alternative-like polarization during bacterial infection.Immunity · 2024Article
- Adipose Tissue Macrophages.Results and problems in cell differentiation · 2024Review
- GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss.Journal of the Chinese Medical Association : JCMA · 2023Article
- TRAF3/STAT6 axis regulates macrophage polarization and tumor progression.Cell death and differentiation · 2023Article
- The neuropeptide CGRP enters the macrophage cytosol to suppress the NLRP3 inflammasome during pulmonary infection.Cellular & molecular immunology · 2023Article
- Application of the neuropeptide NPVF to enhance angiogenesis and osteogenesis in bone regeneration.Communications biology · 2023Article
- Adipose tissue macrophages: implications for obesity-associated cancer.Military Medical Research · 2023Review
- Metabolic impact of adipose tissue macrophages in the early postnatal life.Journal of leukocyte biology · 2022Review
- Central NPFF signalling is critical in the regulation of glucose homeostasis.Molecular metabolism · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 11 institutions in 8 countries.
Funding
Abstract
The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet-fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage-associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs.
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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.