CTRP6 as a negative regulator of anti-inflammatory M2 macrophage polarization
Senthil Kumar J., Kempton E., Mehboob MZ., Lin D., Lei X.
Laboratory Study on Chronic Inflammation, published in Immunometabolism (Cobham) (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
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- Study type
- Laboratory Study
- Journal
- Immunometabolism (Cobham) (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 41159061
- PMCID
- PMC12558006
- DOI
- 10.1097/in9.0000000000000070
Abstract (original English)
Background Chronic low-grade inflammation in adipose tissue, primarily driven by macrophages, plays a central role in obesity pathophysiology. C1q/TNF-related protein 6 (CTRP6), a member of the CTRP family, has emerged as a key regulator of this inflammatory process. Here, we demonstrate that CTRP6 expression is upregulated in adipose tissue macrophages during obesity, where it acts as a potent modulator of macrophage polarization by suppressing M2 polarization. Methods In RAW264.7 macrophages, we distinguished M1 and M2 polarization, induced by lipopolysaccharide (LPS) + interferon-gamma (IFNγ) and interleukin (IL)-4, respectively, by selecting two marker genes for each polarization type from a set of five widely used markers, based on a time-course analysis. We then assessed the effects of recombinant CTRP6 protein treatment on M1 and M2 polarization. Finally, we validated our findings in primary bone marrow-derived macrophages (BMDMs). Results In naïve RAW264.7 macrophages, recombinant CTRP6 protein upregulated M1 marker genes ( Tnf , Nos2 ) while downregulating M2 markers ( Mrc1 , Pparg ). During M1 polarization induced by LPS+IFNγ, CTRP6 treatment had no significant effect. However, during IL-4-induced M2 polarization, CTRP6 not only enhanced M1 markers but also strongly suppressed M2 markers by inhibiting anti-inflammatory signal transducer and activator of transcription
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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