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. 2020 Dec 4;10:21280. doi: 10.1038/s41598-020-77978-z

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Chronic anti-diabetic effect of BR103354 in ob/ob mice. Male ob/ob mice were treated with vehicle or BR103354 (20 and 50 mg/kg) for 4 weeks (n = 13/group). (a) Nonfasting blood glucose levels in ob/ob mice. (b) Plasma FAP activity was measured by fluorometric assay using AMC substrate at week 4. (c) Serum mouse FGF21 levels at week 4 (d) OGTT and AUC in ob/ob mice. (e) Fasting body weight, liver weight and epididymal fat weight from ob/ob mice. (f) Fasting blood glucose, insulin concentrations and HOMA-IR in ob/ob mice. (g) The plasma levels of ALT (GPT), AST (GOT), TG, total cholesterol and NEFA in ob/ob mice. (h) Oil red O staining of the liver from ob/ob mice (Scale bar = 50 µm). (i) Relative expression of genes related to intrahepatic lipogenic gene (GCK), fatty acid and TG synthesis genes (FASN, SREBP and APOC3, LIPIN1), β-oxidation genes (CPT1α, MCAD and PPARα) and FGF21 related genes (ATF4, CHOP, FGF21 and β-klotho) in liver and FGF21 related genes (AdipoQ and β-klotho) in white adipose tissue of ob/ob mice. (j) Immunoblots of p-ERK/ERK of epididymal white adipose tissue lysates from ob/ob mice. The graph shows densitometric quantification of western blot bands. All data are the means ± S.D. *P < 0.05, **P < 0.01 and ***P < 0.001 vs. vehicle group.

Chronic anti-diabetic effect of BR103354 in ob/ob mice. Male ob/ob mice were treated with vehicle or BR103354 (20 and 50 mg/kg) for 4 weeks (n = 13/group). (a) Nonfasting blood glucose levels in ob/ob mice. (b) Plasma FAP activity was measured by fluorometric assay using AMC substrate at week 4. (c) Serum mouse FGF21 levels at week 4 (d) OGTT and AUC in ob/ob mice. (e) Fasting body weight, liver weight and epididymal fat weight from ob/ob mice. (f) Fasting blood glucose, insulin concentrations and HOMA-IR in ob/ob mice. (g) The plasma levels of ALT (GPT), AST (GOT), TG, total cholesterol and NEFA in ob/ob mice. (h) Oil red O staining of the liver from ob/ob mice (Scale bar = 50 µm). (i) Relative expression of genes related to intrahepatic lipogenic gene (GCK), fatty acid and TG synthesis genes (FASN, SREBP and APOC3, LIPIN1), β-oxidation genes (CPT1α, MCAD and PPARα) and FGF21 related genes (ATF4, CHOP, FGF21 and β-klotho) in liver and FGF21 related genes (AdipoQ and β-klotho) in white adipose tissue of ob/ob mice. (j) Immunoblots of p-ERK/ERK of epididymal white adipose tissue lysates from ob/ob mice. The graph shows densitometric quantification of western blot bands. All data are the means ± S.D. *P < 0.05, **P < 0.01 and ***P < 0.001 vs. vehicle group.