Tier 3 — preclinical

Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling

Mi-Young Song, Yong Geun Jeon, Jae Do Yang, Young Jae Moon, Jae Bum Kim, Eun Ju Bae, Byung-Hyun Park
Nature Communications 2026 17(1):57

Bibliography

PubMed
PMID 41495031
DOI
10.1038/s41467-025-66040-z

Study snapshot

DesignMast-cell-specific Sirt6 loss, adoptive-transfer and single-cell transcriptomic obesity study.
ModelDiet-induced obese mice, mast-cell models and human obesity-associated mast-cell SIRT6 expression.
SamplePreclinical cohorts plus human observational tissue/cell-expression context.
InterventionMast-cell Sirt6 depletion; galectin-3 pathway manipulation.
DurationDiet-induced obesity experiments.
EndpointsAdipose inflammation; Fibrosis; Insulin resistance; Weight gain; Galectin-3; M1 macrophage polarization; Single-cell mast-cell states

What the study showed, in plain terms

SIRT6 expression in mast cells fell with obesity in mice and humans. Selective mast-cell Sirt6 loss worsened adipose inflammation, fibrosis and metabolic dysfunction through galectin-3 signaling.

Key findings

SIRT6 deacetylated H3K9 at the Lgals3 promoter, restraining galectin-3 production and fibroinflammatory mast-cell signaling. Loss of this brake worsened obesity-associated adipose dysfunction.

What this study can and cannot tell us

Mostly causal mouse/cell evidence with human observational expression context; does not establish that systemic SIRT6 activation treats obesity or insulin resistance in people.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability