Very few systematic studies are done during the onset and progression of metabolic syndrome in suitable animal models. In this paper we present the effect of High-Fat Simple Carbohydrate (HFSC) feed on the metabolic hormones in C57BL/6J mice to understand the sequence of events leading to impairment of glucose homeostasis. Material and methods: One-month-old male C57BL/6J mice were fed with control (C group) and HFSC (T group) feed (n = 30 each) respectively for five months. The glucose

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... e was studied by Oral Glucose Tolerance Test (OGTT) whereas serum insulin and leptin were quantified using ELISA kits, and serum cortisol was quantified using CLIA kits. Results: Insulin resistance index and HOMA-IR levels were higher in the mice of group T as compared to age-matched mice of group C within one month and significantly higher after and five months of feeding. The total area under the glucose tolerance test curve (AUC) and the insulin curve (AUC ins) was found to significantly increase in the mice of T group as compared to the mice of C group as early as two months of feeding and was elevated after 5 months post feeding. Comparison of the Matsuda index revealed that pancreatic beta cell function was significantly lower in mice of T group as compared to mice of C group by five months of feeding. Leptin levels fluctuated during the 1 st-4 th month and by the 5 th month significant hyperleptinaemia was detected. There was no significant change in cortisol levels in mice of group T as compared to mice of group C after five months of feeding. Conclusions: HFSC feed induces insulin resistance by the first month and progressively impairs glucose tolerance, resulting in hyperlep-tinaemia by the fifth month in male C57BL/6J mice. (Endokrynol Pol 2016; 67 (6): 592-598)