Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice
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ORIGINAL PAPER
Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice Jarinyaporn Naowaboot & Supaporn Wannasiri & Patchareewan Pannangpetch
Received: 16 September 2015 / Accepted: 3 March 2016 # University of Navarra 2016
Abstract Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin
J. Naowaboot (*) Division of Pharmacology, Department of Preclinical Science, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathum Thani 12120, Thailand e-mail: [email protected] S. Wannasiri Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathum Thani 12120, Thailand P. Pannangpetch Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFDinduced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities. Keywords Morin . Obesity . Insulin resistance . Oxidative stress . Inflammation
Introduction Obesity is related to the development of peripheral insulin resistance and is a major etiological factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease [29]. Insulin resistance is an important condition in up-regulating the transcription factor sterol regulatory element binding protein 1c (SREBP1c) [33] and inhibiting β-oxidation of free fatty acid (FFA), leading to enhanced hepatic fat accumulation [28]. SREBP1c plays a key role in regulating fatty acid synthesis, such as
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