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.