p38α blocks brown adipose tissue thermogenesis through p38δ inhibition
Fig 5
p38αFab-KO mice have increased BAT thermogenesis under thermoneutrality conditions.
Fab-Cre and p38αFab-KO mice were fed an HFD for 8 weeks and housed at 30 °C. (A) Body weight time course in Fab-Cre and p38αFab-KO male (8–10-wk-old) mice fed a HFD over 8 weeks. Data are presented as the increase above initial weight (mean ± SEM; Fab-Cre n = 10 mice; p38αFab-KO n = 6 mice). (B) Weight of liver, BAT, eWAT, sWAT, iWAT, and pWAT (mean ± SEM; Fab-Cre n = 10 mice; p38αFab-KO n = 6 mice). (C) Body and skin temperature of surrounding interscapular BAT from HFD-fed Fab-Cre and p38αFab-KO mice (mean ± SEM; Fab-Cre n = 10 mice; p38αFab-KO n = 6 mice). Lower panels show representative infrared thermal images. (D) Immunoblot analysis of UCP1 protein levels in lysates from BAT. Quantification is shown in the lower panel. (E) Fasting and fed blood glucose in Fab-Cre and p38αFab-KO mice fed the HFD at 30 °C (mean ± SEM; Fab-Cre n = 10 mice; p38αFab-KO n = 6 mice). (F) GTT in HFD-fed Fab-Cre and p38αFab-KO at 30 °C. Blood glucose concentration was measured in mice given intraperitoneal injections of glucose (1 g/kg of total body weight) (mean ± SEM; Fab-Cre n = 10 mice; p38αFab-KO n = 6 mice). Statistically significant differences between Fab-Cre and p38αFab-KO mice are indicated: *p < 0.05; **p < 0.01; ***p < 0.001 (t test or Welch’s test when variances were different). See also S1 Data. BAT, brown adipose tissue; eWAT, epididymal fat; GTT, glucose tolerance test; HFD, high-fat diet; IR temperature, infrared temperature; iWAT, inguinal fat; pWAT, perirenal fat; sWAT, subcutaneous fat; UCP1, uncoupling protein 1; WAT, white adipose tissue.