ArticleClinical and translational medicine2026
Chemokine receptor CCR1 restrains adipose tissue remodelling via cAMP/PKA/CREB signalling and adipocyte‒macrophage crosstalk in mice.
Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundAdipose tissue remodelling, encompassing white adipose tissue (WAT) browning alongside brown adipose tissue (BAT) activation, holds promise for combating obesity, yet the endogenous chemokine receptors that restrain this plasticity remain ill-defined. Here, we uncover that C‒C chemokine receptor 1 (CCR1) restrains adipocyte remodelling and energy expenditure.
methodsA high-fat diet (HFD) was provided to systemic and adipocyte-specific Ccr1 knockout mice. The CCR1-selective antagonist BX471 was administered to HFD-fed wild-type (WT) mice as a preventive regimen. Energy expenditure was assessed via indirect calorimetry; BAT thermogenic activity and WAT beiging were quantified through histology and gene expressin analyses. Adipose tissue macrophage homeostasis was analysed via flow cytometry. Peritoneal macrophages were differentiated into either the M1 or M2 state, and conditioned media were applied to the adipocytes.
resultsIn HFD-fed mice, Ccr1 ablation conferred resistance to obesity and insulin resistance, coupled with enhanced WAT browning, augmented BAT thermogenesis and elevated energy expenditure. These metabolic benefits were associated with a shift towards M2 macrophage polarisation and reduced adipose tissue inflammation. Adipocyte-specific Ccr1 knockout recapitulated these phenotypes. BX471 administration in WT mice phenocopied the metabolic effects of Ccr1 deficiency under HFD conditions. Mechanistically, in vitro experiments suggested that Ccr1 loss suppressed Gαi-dependent signalling, leading to increased intracellular cyclic adenosine monophosphate (cAMP) and subsequent protein kinase A/cAMP-response element-binding protein 1 (PKA/CREB) activation, thereby promoting thermogenic gene expression in adipocytes. In addition, conditioned media from M2-polarised macrophages enhanced thermogenic gene expression in adipocytes, and this effect was further potentiated in Ccr1-deficient adipocytes.
conclusionCCR1 regulates adipose tissue remodelling and systemic energy expenditure, at least in part, through cAMP/PKA/CREB signalling and macrophage homeostasis. Pharmacological inhibition of CCR1 attenuates obesity development, suggesting a potential preventive strategy. KEY POINTS: CCR1 expression is significantly elevated in adipose tissue of obese individuals. Systemic and adipocyte-specific Ccr1 deletion promotes fat browning via cAMP/PKA/CREB activation and M2 macrophage polarisation, protecting against obesity. Pharmacological blockade of CCR1 suppresses obesity progression, highlighting its potential as a novel target for metabolic disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.