Kaempferitrin modulates AMPK phosphorylation and PEPCK expression in the liver after a short-term high-fat,high-sucrose diet intervention in mice

Background: Type 2 Diabetes Mellitus is a metabolic disease characterized by hyperglycemia and hyperinsulinemia, closely linked to obesity. According to the International Diabetes Federation, in 2021, almost 6.7 million adults aged 20–79 died due to complications from diabetes. In light of this concerning statistic, novel alternatives, including bioactive compounds such as flavonoids, are undergoing clinical and scientific evaluation to hinder the advancement of metabolic disorders or maybe avert their onset. Aim: We postulate that kaempferitrin may act on glycemic homeostasis in mice challenged with high-fat, high-sucrose diet (HFHS) for 24 h. Methods: Kaempferitrin at a 100 mg/kg dose was administered to two-month-old male C57BL/6 mice challenged with a HFHS diet for 3, 6, or 24 h. Glucose intolerance was assessed by an oral glucose tolerance test (oGTT). In the liver, AMP-activated protein kinase (AMPK) was measured via western blotting, and gene expression of the phosphoenolpyruvate carboxykinase (PEPCK) enzyme was assessed by quantitative PCR (qPCR). Results: At 6 h, kaempferitrin reduced the PEPCK gene expression compared to the group receiving only the HFHS diet. For the 24 h challenge with the HFHS diet, kaempferitrin did not prevent glucose intolerance (oGTT). However, kaempferitrin reduced the pAMPK/AMPK ratio and the PEPCK gene expression compared to the HFHS group. Conclusions: Kaempferitrin, when administered alongside a hypercaloric and hyperlipidic diet, even for short periods, did not prevent glucose intolerance. Nevertheless, it did lead to significant modulations in AMPK phosphorylation and PEPCK gene expression.