Figure 9. Effect of FoxO1 knockdown on hepatic metabolism in db/db mice.

Male db/db mice at 3 months of age were stratified by body weight and randomly assigned to 2 groups (n = 8), which were intravenously injected with FoxO1-RNAi or scrambled RNAi vector at 1.5 × 10¹¹ pfu/kg body weight. Three days after vector administration, mice were fasted for 24 h for the determination of fasting blood glucose (A) and plasma insulin levels (B). Mice were intravenously injected with 500 mg/kg of tyloxapol on day 5 after a 5-h fast. (C) Plasma TG levels were determined at different times. (D) The relative rates of hepatic VLDL production were calculated based on the slopes of plasma TG profiles from C and compared between control scrambled RNAi and FoxO1-RNAi groups. (E) Aliquots of plasma (20 μg protein) 80 min after tyloxapol injection were analyzed by semiquantitative western blot assay using anti-apoB antibody for the determination of plasma apoB secretion. Fasting plasma levels of TG (F), NEFA (G), and cholesterol (H) were determined at day 3 after vector administration. (I) Body weight was determined on day 7. Mice were sacrificed on day 7, and liver tissues were collected for the determination of hepatic protein levels of FoxO1 (J) and MTP (K) as well as hepatic TG content (L). *P < 0.05 versus control.