Figure 2. ASO-Mediated Knockdown of ABHD6 Protects Against High Fat Diet-Induced Obesity.

(A) ABHD6 protein levels in the liver, epididymal white adipose tissue (WAT), and brain of mice treated with either saline, a control non-targeting ASO, or two separate ABHD6 ASOs for 12 weeks.

(B) Body weight in chow-fed or high fat diet (HFD)-fed mice; data represent the mean ± SEM (n = 6-9); * = P < 0.05 (vs. control ASO group within each time point).

(C) Gross appearance of HFD-fed mice.

(D) Gross appearance of epididymal fat pads in HFD-fed mice, and total epididymal fat pad weight in both chow-fed and HFD-fed mice; data represent the mean ± SEM (n = 6-9); * = P < 0.05 (vs. control ASO within each diet).

(E) Body fat % as measured by magnetic resonance imaging (n=4).

(F) Lean body mass as measured by magnetic resonance imaging (n=4).

(G) Snout to anus length (n=10).

(H) Cumulative food intake in ASO-treated mice (n=10).

(I) Total intestinal fat absorption in mice treated with ASOs and fed a HFD for 9 weeks (n=14-15).

(J) qPCR analyses of epididymal adipose tissue (WAT) gene expression in HFD-fed mice; data represent the mean ± SEM (n = 4); * = P < 0.05 (vs. control ASO group). ATGL, adipose triglyceride lipase; HSL, hormone-sensitive lipase, MAGL, monoacylglycerol lipase; SREBP1c, sterol response element-binding protein 1c; FAS, fatty acid synthase; ACC1, acetyl-CoA carboxylase 1; SCD1, stearoyl-CoA desaturase 1; AU = arbitrary units.

(K) Diurnal and nocturnal quantification of physical activity (total beam break counts).

(L) Diurnal and nocturnal quantification of oxygen consumption (VO2).

(M) Diurnal and nocturnal quantification of respiratory exchange ratio (RER; VCO2/VO2). For metabolic cage studies, mice were weight matched and acclimated for at least 48 h prior to measurement. Data represent the mean ± SEM (n = 4); * = P < 0.05 (vs. control ASO).