Fig. 7: Enhanced catecholamine/GDF15/ADRB2 axis in patients with early-stage ALD.

a Serum EPI, NE, and GDF15 levels in healthy controls (n = 7) and alcoholic patients (n = 40) with AWLD (n = 14), AFL (n = 12) and ASH (n = 14) were measured (Supplementary Table 1). b Correlation analyses of serum GDF15 levels with serum EPI or NE levels (n = 7 for healthy controls, n = 40 for alcoholic patients) (Supplementary Table 1). c Stool EPI and NE levels of alcohol patients (n = 18) without or with mild steatosis (n = 9) or moderate steatosis (n = 9) (Supplementary Table 2). d Representative immunoblots for ADRB2, PKA-Cα, GDF15, MAOA, and MAOB in liver tissues of healthy controls and patients with AWLD and AFL (2 blots per group) (Supplementary Table 3). e qRT‒PCR analyses of the liver tissues of healthy controls and patients with AWLD and AFL (n = 3/group) (Supplementary Table 3). f Representative immunoblots for ADRB2, PKA-Cα, and GDF15 in isolated healthy human HEPs treated with 50 mM EtOH and 1 μM CBL for 12 h (3 replicates) (Supplementary Table 3). g GDF15 levels were measured in HEP culture media after 50 mM EtOH and 1 μM CBL treatment for 12 h (n = 3/group) (Supplementary Table 3). h, i Representative H&E and immunostaining of liver sections (h). CD68⁺ macrophages are indicated (blue triangles) and were quantified (i). j, k Healthy human KCs were isolated and treated with LPS (100 ng ml⁻¹), GDF15 (100 ng ml⁻¹), and CBL (1 μM). Representative histogram for the Annexin V apoptosis assay (j) and qRT‒PCR analyses for genes related to the indicated pathways (k) (3 replicates) (Supplementary Table 3). l Schematic diagram of the triciprocal interactions by alcohol-induced dysbiosis. Data are presented as the mean ± SEM. *^,#p < 0.05, **^,##p < 0.01, ***p < 0.001 by Student’s t test or by one-way ANOVA. Scale bars, 50 µm.