A novel aminosterol reverses diabetes and fatty liver disease in obese mice  Nobuhiko Takahashi, Yong Qi, Hiral R. Patel, Rexford S. Ahima  Journal of Hepatology  Volume 41, Issue 3, Pages 391-398 (September 2004) DOI: 10.1016/j.jhep.2004.05.006

Fig. 1 Effects of 1436 on (A) body weight; (B) % body fat; (C) food intake (gm); (D) oxygen consumption (VO2); (E) respiratory quotient, and (F) % liver:body weight, in Lepob/ob mice. Data are mean±SEM, n=8. *P<0.001 vs. vehicle; #P<0.001 vs. 1436. FR—food restricted. Journal of Hepatology 2004 41, 391-398DOI: (10.1016/j.jhep.2004.05.006)

Fig. 2 Effects of 1436 on (A) body weight; (B) % body fat; (C) food intake (gm); (D) oxygen consumption (VO2); (E) respiratory quotient, and (F) % liver:body weight, in wild-type (C57Bl/6J) mice. Data are mean±SEM, n=8. *P<0.01 vs. vehicle; #P<0.05 vs. 1436. FR—food restricted. Journal of Hepatology 2004 41, 391-398DOI: (10.1016/j.jhep.2004.05.006)

Fig. 3 Effect of 1436 on fatty liver. (A) Liver morphology, (B) hematoxylin–eosin stained section and (C) Oil Red O stained section, from wild-type (C57Bl/6J) mouse. Hepatic steatosis in Lepob/ob mice is characterized by massive pale liver (D), and pericentral steatosis in liver sections stained with (E) hematoxylin-eosin and (F) Oil Red O. 1436 decreased liver size (G) and reversed steatosis (H, I). In contrast, weight loss from food restriction (FR) had minimal effect on liver size (J) and steatosis (K, L). Magnification of histologic sections ×100. [This figure appears in colour on the web.] Journal of Hepatology 2004 41, 391-398DOI: (10.1016/j.jhep.2004.05.006)

Fig. 4 (A) FPLC analysis showing VLDL, IDL and HDL cholesterol and (B) triglyceride levels in 1436 or vehicle treated or food restricted (FR) Lepob/ob mice. (C) Plasma triglyceride measured after Tyloxapol treatment was severely reduced by 1436 (8 mg/kg i.p. ×4 doses) treatment but not food restriction. n=6–8, *P<0.0001 vs. vehicle and FR. Journal of Hepatology 2004 41, 391-398DOI: (10.1016/j.jhep.2004.05.006)

Fig. 5 (A, B, C, D) Regulation of FAS, GPAT, CPT-1a and ACOx mRNA expression in Lepob/ob liver by 1436, vehicle or food restriction. (E, F, G, H) Regulation of FAS, GPAT, CPT-1a and ACOx mRNA expression in wild-type (C57Bl/6J) liver by 1436, vehicle or food restriction. n=5. *P<0.001 vs. vehicle; #P<0.001 vs. 1436. Journal of Hepatology 2004 41, 391-398DOI: (10.1016/j.jhep.2004.05.006)

Fig. 6 (A) Effects of 1436 (10 mg/kg i.p. ×1 dose; black circle), food restriction (FR, open triangle) or vehicle (open circle) on whole body insulin sensitivity in Lepob/ob mice. One day later, the mice received an i.p. injection of insulin (0.75u/kg) after 5 h fast. n=4−6, *P<0.001 vs. vehicle and FR. (B) Immunoblot analysis of tyrosine phosphorylation of IRS-1, (C) p85; and (D) ratio of serine phosphorylated Akt to total Akt, in liver lysates from Lepob/ob mice. A bolus of 1 unit insulin or PBS was injected via the portal vein and livers were harvested 2 min later. Data are mean±SEM, n=4; *P<0.001 vs. PBS. Journal of Hepatology 2004 41, 391-398DOI: (10.1016/j.jhep.2004.05.006)