(a-d) 6-month-old WT and Sesn2−/− mice were kept on HFD for 4 months. Livers were analyzed by Oil Red O (ORO) staining (a). ORO densities were quantified (b) (n = 4). Mice were tested for insulin resistance (ITT) (c) (n = 8) and for glucose tolerance (GTT) (d) (n = 8). Area-under-the-curve data for ITT (c) and GTT (d) were calculated. (e-h) 5-month-old Sesn2−/− mice kept on HFD for 3 months were transduced with AAV-Con (n = 4) or AAV-Sesn2 (n = 3). After 10 days, livers were harvested from the treated mice and analyzed by ORO staining (e). ORO densities were quantified (f). Mice were tested for insulin resistance at 5 days (g) and for glucose tolerance at 7 days (h) after AAV transduction. Area-under-the-curve data for ITT (g) and GTT (h) were calculated. (i-l) 5-month-old Sesn2−/− mice kept on HFD for 3 months were daily injected with vehicle (PBS, n = 4) or TUDCA (500 mg per kg body weight per day i.p., n = 5). After 10 days of treatment, livers were harvested from the treated mice and analyzed by ORO staining (i). ORO densities were quantified (j). Mice were tested for insulin resistance at 5 days (k) and for glucose tolerance at 7 days (l) after initiation of TUDCA treatment. Area-under-the-curve data for ITT (k) and GTT (l) were calculated. Scale bars, 200 μm; 10 μm (insets). All data are shown as the mean ± s.e.m. P values are from Student’s t test.