Figure S2.

Mmp12/IR-ATM signature and Mmp12 blockade in mice. (A) Overview of the meta-analysis of single cell transcriptome analysis to derive Mmp12 meta-signature. The eight chosen datasets with CD45⁺ cells expressed Mmp12 in a subset of the cells. The meta-correlation analysis and meta-differential expression analysis from each dataset (detailed in Materials and methods) led to identification of a gene signature specific to these subsets of Mmp12⁺ cells. (B) The cell type identification using the Mmp12 meta-signature genes with scQuery showing highly significant macrophages as the primary cell type with this signature. (C) Mmp12 meta-signature enrichment in (left) WAT of SPF mice compared to GF mice under HFHS condition (P value <0.001) and (right) WAT of SPF mice compared to GF mice under ND condition (not significant). (D) Top: GTT (left) and insulin tolerance test (right) in HFHS-fed wild type and Mmp12 knockout SPF mice (mean ± SEM; n = 10; one-tailed parametric t test, *P < 0.05, **P < 0.01). Bottom: GTT and 2 h (120 min) blood glucose (measured after 2 h of intraperitoneal glucose injection) in HFHS-fed SPF or GF mice injected with Mmp12 inhibitor, MMP408 (mean ± SEM, one-tailed parametric t test, n = 12 for SPF mice, n = 5 for GF mice (two-tailed), *P < 0.05, **P < 0.01).