Summary of <i>in vivo</i> studies performed in mice.

<p>Summary of <i>in vivo</i> studies performed in mice.</p

Efficacy of PTM in non-human primates (NHPs).

<p>A–C: Inhibition of <i>de novo</i> 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.</p

Parallel comparison of PTM and CPT1 inhibitor on glucose and lipid metabolism in perfused liver of lean C57BL/6 mice.

<p>PTM and CPT1 inhibitor are used at 100 μM in the perfusion media (n = 3–5 per group). Bars represent means ± SEM. Asterisks denote statistical significance of treatment group compared to control. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.</p

Platensimycin inhibits enzymatic activity and expression of fatty acid synthase (FAS) and lipogenic genes.

<p>A: Effect of PTM on FAS enzymatic activity in the liver of eDIO mice treated with PTM (100 mpk, BID, p.o. for 4 days) determined by Malonyl-CoA dependent consumption of NADPH (n = 7–8). B–C: Protein level of FAS in the liver determined by western blot and quantitated by Li-COR. D: Relative RNA levels of FAS, sterol regulatory element-binding transcription factor 1 (SREBP-1c), liver X receptor alpha (LXRα), and carbohydrate-responsive element-binding protein (ChREBP) in the liver determined by quantitative RT-PCR. Bars represent means ± SEM. Asterisks denote statistical significance of treatment group compared to vehicle group. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.</p

Effect of Platensimycin on body weight gain and food intake in different mouse models.

<p>A–C: Subchronic treatment of PTM in eDIO mice (40, 125, and 400 μg/h, minipump for 10 days) (n = 8). D–E: Chronic treatment of PTM in <i>db/+</i> mice on high fructose diet (3, 10, 30, and 100 mpk in drinking water for 29 days) (n = 8). F–H: Subchronic treatment of PTM in <i>db/db</i> mice for 16 days (3, 10, and 30 mpk, BID, p.o. for 16 days). Bars represent means ± SEM. Asterisks denote statistical significance of treatment group compared to vehicle group. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.</p