Undergraduate Thesis Or Project
 

Xanthohumol derivatives improve insulin sensitivity in obese mice

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https://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/0r9675510

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  • Metabolic syndrome, characterized by a collection of risk factors including abdominal obesity, insulin insensitivity, elevated plasma triglycerides, hypertension and low plasma high-density lipoproteins (HDLs), is a major contributing factor to the development of cardiovascular diseases and type II diabetes (T2D). Xanthohumol (XN), a flavonoid isolated from Humulus lupulus cones, has been shown to reduce some markers of metabolic syndrome by a proposed mechanism of mitochondrial uncoupling (Legette et al, 2012 and Kirkwood, et al, 2013). Two XN derivatives, dihydroxanthohumol (DXN) and tetrahydroxanthohumol (TXN) appear to have a more profound effect on mitochondrial uncoupling in vitro, but their effect in vivo is unknown. Male C57BL/6J mice were fed a high fat diet (60% kcal fat, 20% kcal protein and 20% kcal carbohydrate) supplemented with XN, DXN or TXN at a dose of 30 mg/kg body weight/day for 14 weeks. Insulin resistance was measured via glucose tolerance assays (GTT) during weeks 4 and 11, where plasma glucose levels were measured at 15, 30, 60 and 120 minutes following an intraperitoneal glucose injection of 2 g/kg body weight. Body weights were measured weekly, and plasma glucose, insulin, triglycerides, and cholesterol were examined following blood collection at sacrifice after 14 weeks on test diets. All mice in XN, DXN and TXN treatment groups showed improved insulin sensitivity demonstrated by smaller increases and more rapid recovery of blood glucose level compared to control (vehicle-diet) mice in the GTT. Only TXN mice showed significantly reduced fasting plasma glucose and insulin levels compared to the control, and none of the three compounds reduced plasma triglycerides or cholesterol levels. Mice given TXN showed significantly reduced weight gain compared to control mice (p<0.05), though mice given DXN also displayed a reduction in weight gain to a lesser extent. These results suggest that XN, DXN and TXN have a protective effect against metabolic syndrome by improving insulin sensitivity and glucose metabolism.
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  • Linus Pauling Institute, USDA, Hopsteiner
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file details Hay Josh - Thesis XN Mouse Study Josh Hay (final 06-10-15).pdf 07/26/2017 Public
file details Hay Josh - XN seminar.pptx 07/26/2017 Public