Figure 7: Inhibition of hepatic mTORC1/S6K pathway ameliorates obesity-related hypertriglyceridemia.

(a) Immunoblotting of liver extracts from ob/ob mice and their lean control C57BL/6 mice with anti-phospho-p70-S6K, p70-S6K, phospho-S6 or S6 antibodies. (b) Serum TG levels were measured in ob/ob (black bars) and control (white bars) mice under 10 h-fasted or -fed conditions (n=5–7). (c) LPL mRNA expressions in WAT were examined (n=8–9). (d–k) DN-S6K (black bars) or LacZ (white bars) adenovirus was administered to ob/ob mice. (d) Liver extracts were immunoblotted with anti-p70-S6K, phospho-S6 or S6 antibodies. Serum TG levels were measured (e) and sera in fed states were analysed by HPLC (f) on day 5 after adenovirus administration (e; n=4–5, f; n=4–7). The rates of hepatic TG secretion were determined (g), and fat-tolerance tests were performed (h) (g; n=4–7, h; n=5). Plasma LPL activity (i), LPL mRNA expressions in WAT (j) and TG-hydrolysis activity in WAT (k) were determined on day 5 after adenovirus administration (i; n=6, j; n=7–11, k; n=6–7). (l–n) DN-S6K (black bars) or LacZ (white bars) adenovirus was administered to KK and KK-Ay mice. Serum TG levels (l) and LPL mRNA expression in WAT (m) were determined on day 5 after adenovirus administration (l; n=4–7, m; n=4–7). (n) TG-clearance studies were performed (n=5). The representative images derived from at least two experiments were displayed (a and d). Data are presented as means±s.d. *P<0.05, **P<0.01 by the unpaired t-test. NS, not significant.