Experimental protocol (A). Placement of icv cannulae occurred on day 0 (3 weeks before the in vivo study), and venous and arterial catheters were placed on day 14. Following recovery from the surgery (day 17), rats were divided in 3 groups: SC, OF, and PF. On the evening prior to the pancreatic-insulin clamp, all rats received a fixed portion of calories (80 kcal) to ensure a comparable post-absorptive state at the start of the metabolic experiments. (B) Pancreatic-insulin clamp. Rats received icv infusion of the pharmacologic inhibitor of CPT1A or its inactive stereoisomer for 6 hours before and during the clamp (see Methods). (C) Glucose infusion rate during the clamp in SC, PF, and OF rats. (D) Suppression of glucose production during the clamp period express as percent decrease from basal glucose production. Central inhibition of fatty acid oxidation markedly suppressed G6Pase flux (E), gluconeogenesis (F), and the expression of key genes involved in glucose metabolism, G6Pc (G) and Pck1 (H). *P < 0.05 versus control.