Pharmaceutical inhibition of p38α reduces adiposity and enhances the browning of WAT.

Abstract

<p>(A and B) Representative HE staining of iBAT, iWAT, and eWAT (A), diameter and cross-sectional area (B) of adipocytes in these adipose tissues from SB203580-treated C57BL/6J mice at 2 d postinjection. Bars: 100 μm. See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. (C) BW of C57BL/6J mice before and after 4 wk of SB203580 treatment (control: <i>n</i> = 4, SB203580: <i>n</i> = 5). See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. (D and E) Relative weight of iWAT and eWAT from C57BL/6J mice after 4 wk of SB203580 treatment. These mice were maintained at RT (D, <i>n</i> = 5 per group) or exposed to cold for 2 d before analysis (E, <i>n</i> = 5 per group) as indicated. See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. (F) Relative mRNA levels of UCP-1, PGC1α, ELOVL3, and DIO2 in iWAT from C57BL/6J mice after 4 wk of SB203580 treatment (<i>n</i> = 10 per group). These mice were exposed to cold for 2 d before analysis. See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. (G) Representative western blots of p-CREB (Ser133) and UCP-1 in iWAT from C57BL/6J mice after 4 wk of SB203580 treatment. These mice were exposed to cold for 2 d before analysis. (H and I) Representative PET/CT images (H) and PET images (I) of C57BL/6J mice after 4 wk of SB203580 treatment. These mice received a daily CL316,243 injection for 8 d before ¹⁸F-FDG injection. White dashed triangles represent the anatomical sites of iWAT. (J) Ex vivo measured ¹⁸F-FDG uptake in iBAT, iWAT, and eWAT to tissue weight ratio by γ counter (<i>n</i> = 3 per group). See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. (K) Relative weight of iWAT from <i>db/db</i> mice after 3 wk of SB203580 treatment (<i>n</i> = 5 per group). See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. (L and M) Representative HE staining of iWAT (L), diameter and cross-sectional area of adipocytes in iWAT (M) from <i>db/db</i> mice after 3 wk of SB203580 treatment. Bars: 100 μm. See also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004225#pbio.2004225.s010" target="_blank">S1 Data</a>. Means ± SEM are shown. *<i>p</i> < 0.05; **<i>p</i> < 0.01; ***<i>p</i> < 0.001. BW, body weight; CREB, cAMP-response element binding protein; CT, computed tomography; DIO2, deiodinase 2; ELVOL3, elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3; eWAT, epididymal white adipose tissue; HE staining, hematoxylin-eosin staining; iBAT, interscapular brown adipose tissue; iWAT, inguinal white adipose tissue; NS, not significant; PET, positron emission tomography; PGC1α, peroxisome proliferative activated receptor gamma coactivator 1α; RT, room temperature; UCP-1, uncoupling protein 1; WAT, white adipose tissue.</p