Extended Data Fig. 2: Derivation of Mural-Tlr4^KO mice and systemic phenotype following high fat diet feeding.

a) Mural-Tlr4^KO (Pdgfrb^rtTA; TRE-Cre; Tlr4^loxP/loxP) mice were generated by breeding the Pdgfrb^rtTA transgenic mice to animals expressing Cre recombinase under the control of the tetracycline-response element (TRE-Cre) and carrying floxed Tlr4 alleles (Tlr4^loxP/loxP). Littermates carrying only Pdgfrb^rtTA and Tlr4^loxP/loxP alleles (i.e. Cre-) were used as the control animals (Control). The addition of doxycycline (Dox) leads to inactivation of Tlr4 in Pdgfrb-expressing cells.

b) Intraperitoneal glucose tolerance tests (GTT) of RT-housed Control (n=9) and Mural-Tlr4^KO (n=6) mice after HFD feeding. * denotes p< 0.05 by unpaired two-tailed Student’s t-test.

c) Intraperitoneal insulin tolerance tests (ITT) of RT-housed Control (n=9) and Mural-Tlr4^KO (n=6) mice after HFD feeding. * denotes p< 0.05 by unpaired two-tailed Student’s t-test.

d-f) Levels of total monocytes and pro-inflammatory monocytes (LY6C+) in blood (d), bone marrow (e), and spleen (f) of Control (n=8) and Mural-Tlr4^KO (n=8) mice after 5 months of HFD feeding. Bars represent mean ± s.e.m.

Exact p values can be found in Source Data Extended Data Figure 2. Data were reproduced two times in independent experiments.