Alteration of Liver MMP-9/TIMP-1 and Plasma Type IV Collagen in the Development of Rat Insulin Resistance
Insulin resistance (IR) is a risk factor of many diseases and present in various metabolic abnormalities including obesity, type 2 diabetes. Although several factors are believed to contribute to the initiating course of IR, fatty liver, hepatic injury or hepatic fibrosis is a prominent feature during IR development. Although a correlation between IR and hepatic injury has long been suspected, it remains unclear whether accumulation of fat in the liver is causally related to hepatic injury which in turn induces systemic IR. Using rat IR model with high-fat diet (HFD), the present study shows a time courses of expression of matrix metalloproteinases (MMP-9)/tissue inhibitors of metalloproteinases (TIMP-1) mRNA and protein in the liver as well as plasma type IV collagen (collagen-IV), and liver histology. The results showed that expression of MMP-9 mRNA and protein significantly increased in rat liver after 15 days in HFD group but decreased thereafter. In contrast, liver TIMP-1 and plasma collagen-IV levels gradually increased and reached to a peak at the end of 60 days in HFD group. Histological analysis revealed that livers from HFD group exhibited steatosis, and more collagen fibers were formed in the interspace among disse cavea and intruded into the tight junctions among hepatocytes detected by transmission electron microscope. The results indicated that the IR induced alteration of MMP-9 to TIMP-1 ratio may play a role in elevation of collagen-IV, which may participate in development of inchoate hepatic fibrosis in the later course of IR.
KeywordsInsulin resistance Hepatic steatosis Hepatic fibrosis Type IV collagen MMP-9/TIMP-1
The work was supported by grants from the Scientific Technological Research Planning of Shaanxi Province (2010K15-05-04). We also acknowledged the assistance from the Electronic Microscope Center of the Fourth Military Medical University.
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