Extended Data Fig. 7: IL-17A phosphorylates PPARγ in adipocytes to promote obesity. | Nature Metabolism

Extended Data Fig. 7: IL-17A phosphorylates PPARγ in adipocytes to promote obesity.

From: Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice

Extended Data Fig. 7

a, FITC-dextran in plasma from ND- or HFD-fed-38-week-old C57BL/6 mice (beginning at 8 weeks), treated wit or /without digoxin (beginning at 20 weeks) (n = 5 mice per group; P = 0.0019). b, Daily faecal mass in mice from a (n = 3, 4, 5, and 6 mice; p <0.0001). c, Faecal caloric density measured by bomb calorimetry in mice from a (n = 4 mice per group). d, Faecal trycerides (TGs) (n = 6, 5, 6, and 5 mice per group), proteins (n = 5 mice per group) and carbohydrates (n = 5, 4, 4, and 5 mice) in mice from a. e, Plasma free fatty acids (FFA) in mice from a (n = 5, 6, 5, and 7 mice). f, qRT-PCR of target genes for hepatic β oxidation in livers of mice from a (n = 5, 4, 5, and 7 mice). g, H&E in gWAT of mice from a (upper panel) and of ND- or HFD-fed-38-week-old Il17ra+/+ and -Il17raΔ/Δ mice (lower panel). Scale bar, 100 μm. h, Adipocyte size of mice from a (n = 7, 4, 8, and 7 mice; P = 0.0005; 0.0178; 0.0238, from left to right). i, Adipocyte size of ND- or HFD-fed-38-week-old Il17ra+/+ and Il17raΔ/Δ mice (n = 4, 4, 5, and 3 mice; P = 0.0463; 0.0043; 0.0029, from left to right). j, Scheme of fasting-refeeding and sample collection in ND- or HFD-fed-24-week-old C57BL/6 mice (beginning at 8 weeks, treated with or without digoxin (beginning at 20 weeks) for 1 month. k, l, Pc j after 24 hours of fasting and refeeding represented as ng/ml (k) (p <0.0001; 0.0053) or normalized to fasted levels (T0) (l) (P = 0.0083; 0.0181; 0.0047; 0.0475; 0.0176; 0.0376; 0.0478, from left to right) (n = 5 mice per group). m, Scheme of Il17raΔ/Δ(Adipoq) mouse model in which IL17ra deletion is controlled by Adipoq-Cre. n, Il17ra mRNA levels in WAT from HFD-fed-20-week-old Il17ra+/+(Adipoq) and Il17raΔ/Δ(Adipoq) mice (beginning at 8 weeks) (n = 5 mice per group; P = 0.05; 0.0218, from left to right). o, Weights of HFD-fed-20-week-old Il17ra+/+, Il17raΔ/Δ, Il17ra+/+(Adipoq) and Il17raΔ/Δ(Adipoq) mice (beginning at 8 weeks) (n = 8, 7, 8, and 6 mice; p <0.0001; 0.0026, from left to right). p, Total lean mass in mice from n (n = 6, 4, 8, and 4 mice; P = 0.0092; 0.0244, from left to right). q, Liver weight in mice from n (n = 6, 4, 8, and 6 mice; P = 0.028; 0.0007, from left to right). r, BMD in mice from n (n = 6, 4, 8, and 6 mice). s, qRT-PCR in gWAT from mice from n (n = 4 mice per group). t, u, qRT-PCR of target genes for lipogenesis (t) (P = 0.008; 0.0408; 0.0128; 0.0064, from left to right) and differentiation (u) (P = 0.0228; 0.0462, from left to right) in gWAT of mice from a (n = 6, 4, 7, and 7 mice). v, qRT-PCR of genes modulated by the CDK5-mediated phosphorylation of PPARγ on Ser273 in differentiated 3T3-L1 adipocytes (n = 3 independent experiments; P = 0.0442; 0.0129; 0.0033, from left to right). w, qRT-PCR of genes modulated by the CDK5-mediated phosphorylation of PPARγ on Ser273 in gWAT from mice from a (n = 6, 4, 7, and 7 mice; p <0.0001; 0.0094; 0.0002; 0.0007; <0.0001; 0.0086; 0.0004; 0.0284; 0.0002; 0.0489; <0.0001; 0.0216; 0.0001; 0.0038; 0.0002; 0.0386, from left to right). Unpaired two-tailed Student’s t test (a-f, h, i, l, n-w) or two-way ANOVA (k) were used. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001. Data are represented as means ± s.e.m.

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