In Vivo Effect Of Intracerebroventricularly NESFATIN-1 On Insulin Sensitivity And Glucose-Lipid Metabolism In Insulin-Resistant Rats Induced By High-Fat Diet

Objective To investigate the effect of nesfatin-1(1-82) recombinant proteins given hypothalamic on insulin sensitivity and glucose-lipid metabolism in insulin-resistant rat model induced by high-fat diet.Method Male Sprague-Dawley (SD) rats were randomly divided into chow diet fed with artificial cerebrospinal fluid infusion aCSF group (NC group, n=15), high fat diet fed with aCSF group (HC group, n=15), and high fat diet fed with nesfatin-1 recombinant protein group (HN group, n=15). Glucose-lipid metabolism and insulin sensitivity were evaluated by hyperinsulinemic-euglycemic clamp technique with [3-3H]glucose and 2-deoxy-3H glucose (3H-2DG) as the tracer in conscious rats.Results Weight, Lee's index, HOMA-IR, fasting plasma insulin (PIns), free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels were significantly increased in high fat-fed rats groups (P<0.05 or P<0.01); while ISI and high-density lipoprotein cholesterol (HDL-C) was significantly decreased in high fat-fed rats groups (all P<0.05). During the clamp steady-state, glucose infusion rate (GIR) in HN group was significantly increased compared to HC group, but still significantly lower than that in NC group (17.77±2.06 vs. 10.07±1.62 and 23.03±1.75 mg.kg-1.min-1, all P<0.01). And the suppression of hepatic glucose production (HGP) inhibited by insulin infusion in HC group, HN group and NC group were 29%, 38.5% and 50% respectively (all P<0.01). The glucose uptake rate (MGU) of soleus muscle in NC and HN group were 3.2 times and 1.1 times higher than that in HC group (4.81±0.73 and 2.39±0.42 vs 1.49±0.14μmol·100g-1·min-1, all P<0.01), respectively. And the MGU of gastrocnemius muscle in NC and HN group were 3.3 times and 1.7 times of HC group (1.70±0.37 and 0.89±0.22 vs 0.51±0.10μmol·100g-1·min-1, P<0.01 and P<0.05), respectively.Conclusion Insulin resistance induced by high-fat diet in rats was improved by, at least partially, micro-infusion of nesfatin-1 recombinant protein intracerebroventricularly.