Figure 2. Adipose SWELL1 ablation augments lipolysis and hormone sensitive lipase activation.

(A) Percentage decrease in total fat in high-fat (HF) diet (6–9 months) WT and Adipo-KO mice (males) after switching to regular chow (RC) diet for 4 weeks estimated by NMR. (B) Total body weight of WT (n = 7) and Adipo-KO (n = 8) mice (males) fed with GAN diet for 22 weeks. (C) Body composition for total fat and lean mass estimated by EchoMRI from mice in B at 22-week time point of GAN diet. (D) Random plasma NEFAs and glycerol normalized to total fat mass of WT and Adipo-KO mice in B. (E) mRNA expression of CD36 and PLIN relative to GAPDH in eWAT isolated from WT and Adipo-KO (n = 8 each, males) mice on GAN diet for 22–25 weeks. (F and G) Ex vivo lipolysis assay measuring NEFA (F) and glycerol (G) released from eWAT of WT (n = 9 experimental replicates from 3 mice) and Adipo-KO mice (n = 8 experimental replicates from 3 mice) at 30, 60, 90, and 120 minutes under basal, unstimulated conditions. (H and I) Ex vivo lipolysis assay measuring NEFA (H) released from WT and Adipo-KO (n = 11–12 experimental replicates from 2 mice/group) mice on HFD for 5 weeks at 30, 60, 90, and 120 minutes upon stimulation with 50 nM isoproterenol and the corresponding rate of NEFA production (I). (J) Western blots for protein levels of SWELL1, p-HSL, total HSL, and β-actin from primary adipocytes isolated from SWELL1^fl/fl mice transduced with either Ad-GFP or Ad-Cre-GFP to generate WT and SWELL1-KO primary adipocytes and treated with either vehicle or 100 nM isoproterenol for 15 minutes and the corresponding densitometry analysis. Data are represented as mean ± SEM. Two-tailed unpaired t test was used in A–E and I. Two-way ANOVA was used in F–H. One-way ANOVA was used in J. *, **, and *** represent P < 0.05, P < 0.01, and P < 0.001, respectively.