The Fatty Acid Synthase Inhibitor Platensimycin Improves Insulin Resistance without Inducing Liver Steatosis in Mice and Monkeys
Fig 5
Efficacy of PTM in non-human primates (NHPs).
A–C: Inhibition of de novo lipogenesis (DNL) by PTM in lean cynomolgus monkeys (A) (n = 5 for vehicle and 4 for PTM) and rhesus (B) (n = 4), and lean aged rhesus monkey (C) (n = 6). Animals were dosed with PTM (60 mpk BID p.o. in A and B, 20 and 60 mpk BID s.c. in C and blood samples were collected at 24 hrs post dosing. D: Effect of PTM on DNL of lean rhesus monkeys (60 mpk, p.o.). E–J: Effect of chronic treatment of PTM on body weight (E), fasting glucose levels for predose (F) and 2 hrs post dose at baseline, day 9 and day 22 (G) and insulin (H–I). PTM was dosed at 60 mpk mixed with yogurt for 28 days. J: Liver fat fraction was determined by MRS imaging at baseline and after 28 days of s.c. dosing of PTM (100 mpk, BID) in lean rhesus monkeys. Bars represent means ± SEM. Asterisks denote statistical significance of treatment group compared to vehicle or baseline. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.