Extended Data Fig. 10: Other responses of primed mice and cells to obesogenic stimuli.
From: Adipose tissue retains an epigenetic memory of obesity after weight loss
a, Glucose uptake of isolated, cultured primary adipocytes from ingAT from CC_s and HC (left) and CCC and HHC (right) mice. Each dot represents an individual biological replicate of a pool of 3 mice. b,c, AdipoRed signal of dividing SVF (MM), SVF stimulated with 10 nm insulin only (MM + Ins) and induced SVF with 10 nm insulin (IMM + Ins) 10 days after induction/no induction of differentiation from epiAT (b) and ingAT (c) SVF from CC_s, HC, CCC and HHC mice. Each dot represents an individual biological replicate of a pool of 3 mice. Every SVF pool was tested in all three conditions. d, GTT of HCH and CCH mice; blood glucose levels (n = 5 each). e, AOC of GTTs from d. f, ITT of CCH and HCH mice; blood glucose levels (n = 5 each). g, AOC from ITTs from e. h, Distribution of epiAT adipocyte area. (n = 4 mice each, 10 pictures each). i, Representative images of liver HE stained sections from CCH and HCH, 20x magnification, scale bar 200 μm. j, Liver tg per μg liver tissue (C&H:n = 6 each, CC_s: n = 10, HC: n = 9, CCH: n = 11, HCH: n = 12, from 2-3 experiments). Boxplot represents minimum, maximum and median. k, Pathological scoring of liver sections per group (n = 4 each). l, UMAP of 15,665 nuclei representing epiAT pools (n = 5 pooled mice each) from CCH and HCH split by condition. m, Relative abundance of macrophage subclusters. n,o, Top significant pathway terms from upregulated (n) and downregulated (o) HCH DEGs that are explained by the epigenetic state in HC adipocytes based on Reactome database. (Fisher’s exact test, adjusted p-value < 0.05 by the Benjamini-Hochberg method for correction). Significance was calculated between age matched controls and experimental groups. Significance for a, e, g, was calculated using two-tailed Mann-Whitney tests. Significance for b, c was calculated using unpaired, two-tailed Student’s t-tests with Welch’s correction and Benjamini, Krieger, and Yekutieli correction for multiple testing. Significance for j was calculated using unpaired two-tailed Student’s t-tests with Welch’s correction. Error bars represent s.d. APCs, adipocyte progenitor cells; DCs, dendritic cells; EpiCs, epithelial cells; EndoCs, endothelial cells; FIPs, fibro-inflammatory progenitors; LECs, lymphatic endothelial cells; MastCs, mast cells; MesoCs, mesothelial cells; SMCs, (vascular) smooth muscle cells; NPVMs, non-perivascular macrophages; LAMs, lipid-associated macrophages; PVMs, perivascular macrophages; P-LAMs, proliferating LAMs.
