Fig. 3: Adipocyte lipolysis mediates GDF15 secretion from alternatively activated M2-like macrophages through fatty acids.
a, Top: t-distributed stochastic neighbour embedding plot of stromal vascular cells from gWAT of mice treated with CL for 3 days. Clustering identified ten major cell types or states. cDCs, conventional dendritic cells; NKT, natural killer T; NK, natural killer; VECs, vascular endothelial cells. Bottom: data were queried for cell clusters expressing Gdf15. exp., expression. b, Heat map showing the expression of Gdf15 and other cell-identifying factors in the various cell populations identified in scRNA-seq data. c, Data were queried to determine Gdf15 expression in the identified macrophage populations. d, Median normalized average Gdf15 expression in the M2-like, M1-like and macrophage populations from CL-treated mouse scRNA-seq data. The box-and-whisker plot is defined by the median (centre line) with the first quartile (Q1, lower line), third quartile (Q3, upper line), maximum (Q1 − 1.5 × interquartile range) and minimum (Q3 + 1.5 × interquartile range). Whiskers: 1.5 × (Q3 − Q1). P values were calculated using a one-way ANOVA with Benjamini–Hochberg correction for multiple tests. e, Gdf15 expression in mouse F4/80+ and F4/80− fractions (n = 3 per group). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. f, Experimental schematic of the isolation, activation and treatment of BMDMs. g, GDF15 levels in medium from BMDMs treated with fatty acids (n = 3) or tunicamycin (n = 2). Individual data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. h, Gdf15 expression in BMDMs treated with fatty acids (n = 3) or tunicamycin (n = 2). Data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. i, GO enrichment analysis of M1- and M2-like macrophage populations from scRNA-seq data. The P-adj was calculated using the Benjamini–Hochberg method. j, GDF15 levels in medium from M2-like BMDMs treated with rosiglitazone (Rosi) or T0070907 (T007) (n = 9 per group). Individual data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a one-way ANOVA with post hoc testing and Tukey’s correction. k, GDF15 levels in medium from M2-like BMDMs treated with palmitate (Palm) or T0070907 (T007) (n = 9 per group). Individual data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a one-way ANOVA with post hoc testing and Tukey’s correction. f created using BioRender.com.
