Adiponectin Activates AMPK Signaling Via Regulating LKB1 Expression In Liver Tissues Of SD Rats

Background:The AMP-activated protein kinase (AMPK) acts as a sensor of cellular energy status. Once activated, AMPK switches on catabolic pathways that generate ATP. while switching off ATP-consuming processes. It appears to play a key role in maintaining energy balance at the whole body level. Adiponectin, derived mainly from adipose tissue,regulates glucose and fatty acid metabolism and has anti-inflammatory and anti-atheorscleroticp roperties. AMPK is the key molecule in adiponectin signaling pathway. Tumor suppressor LKB1 which is the upstream AMPK kinase can phosphory-late AMPK at Thrl72. It is associated with the heat-shock protein 90 (Hsp90) chaperone and the Cdc37 kinase-specific targetting subunit for Hsp 90. Binding with Hsp90 and Cdc37 is necessary for LKB1 stability. Radicicol,a class of Hsp90 inhibitor.is macrolide antibiotic. It combines with Hsp90 and interferes with its function, thus affecting the stability of LKB1. Adiponectin and LKB1 play an important role on regulating AMPK.Objective:To investigate whether adiponectin activates AMPK to mediate metabolism by up-expressing LKB1 in rats liver tissues.Methods:Total 30 male Sprague-Dawley (SD) rats were randomly divided into two groups and received either a rat maintenance diet (Control group) or high-fat diet (HF group) for 16 weeks. We determined respectively the levels of adiponectin in serum, AMPKα, phospho-AMPKα(P-AMPKα) and phospho-LKB1(P-LKB1) in liver tissues. Metabolic parameters of the rats were also performed. In addition, the expression of AMPKa, P-AMPKa and P-LKB1 were measured in primary hepatic cells which were treated of adiponectin or pretreated of radicicol. Every condition was repeated three times.Results:(1) In the SD rats.16 weeks of high-fat feeding induced obesity and increased triglyceride (TG),total cholesterol (TCH), free fatty acid (FFA), fasting blood glucose (FBS) and free insulin (FINS) (All P<0.05). (2) The obese rats possesed the lower adiponectin level in serum (P<0.05). (3) 16 weeks of high-fat treatment lead to a significant decrease of P-AMPKa protein contents (P<0.05). while it did not alter AMPKa protein levels (P>0.05). (4) Protein levels of P-LKB1 also diminished after high-fat feeding (P<0.05). (5) Serum total adiponectin was positive relation with P-AMPKa, as well as P-LKB1,but negatively correlated with BW, FFA, TG and FPG, (P<0.05 for all). (6) In primary liver cells, adiponectin up-expressed P-LKB1(P<0.05). (7) And adiponectin activated AMPKa in primary liver cells, while after radicicol pretreated cells, the effect induced by adiponectin were dramaticly hindered (P<0.05).Conclusion:Impaired adiponectin which was induced by high-fat feeding decreased P-LKB1 expression, resulting in down-regulating the activity of AMPKa in obese SD rats liver.