Effect and the probable mechanisms of silibinin in
regulating insulin resistance in the liver of rats with non-alcoholic fatty
liver |
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Authors: | Jiayin Yao Min Zhi Xiang Gao Pinjin Hu Chujun Li Xiaobo Yang |
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Institution: | Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People''s Republic of China |
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Abstract: | Our previous study has shown that reduced insulin resistance (IR) was one of the
possible mechanisms for the therapeutic effect of silibinin on non-alcoholic
fatty liver disease (NAFLD) in rats. In the present study, we investigated the
pathways of silibinin in regulating hepatic glucose production and IR
amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided
into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD +
silibinin group (high-fat diet + 0.5 mg kg-1·day-1
silibinin, starting at the beginning of the protocol). Both subcutaneous and
visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR),
intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were
performed. The expression of adipose triglyceride lipase (ATGL) and of genes
associated with hepatic gluconeogenesis was evaluated. Silibinin intervention
significantly protected liver function, down-regulated serum fat, and improved
IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly
prevented visceral obesity by reducing visceral fat, enhanced lipolysis by
up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating
associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and
glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats.
Reduction of visceral obesity, enhancement of lipolysis and inhibition of
gluconeogenesis might be the underlying mechanisms. |
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Keywords: | Non-alcoholic fatty liver disease Insulin resistance Silibinin Visceral obesity |
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