The effect of caffeic acid and intermittent fasting on inflammation and Leptin/Obrb/SOCS3 pathway in rats fed with high-fructose

THE EFFECT OF CAFFEIC ACID AND INTERMITTENT FASTING ON INFLAMMATION AND LEPTIN/Obrb/SOCS3 PATHWAY IN RATS FED WITH HIGH-FRUCTOSE Aim: This study aimed to investigate the effects of caffeic acid (CA) and intermittent fasting (IF) on inflammation (TNF-α and IL-6) and hypothalamic leptin/Obrb/SOCS3 signaling pathways in rats subjected to long-term high fructose consumption. Materials and Methods: A total of 56 male Sprague-Dawley rats aged 9–10 weeks were used in the study. The animals were divided into eight groups (n=7 per group): Control (C), CA, IF, CA+IF, Fructose (F), F+CA, F+IF and F+CA+IF. For the first 6 weeks, drinking water containing 20% fructose solution was given to the fructose groups, while the other groups received plain drinking water. All groups had ad libitum access to standard chow. Starting from the sixth week, CA (50 mg/kg/day orally via gavage) and IF (16-hour of fasting and 8-hour of feeding daily) were applied to the relevant groups for a duration of 8 weeks. Body weight, weekly food (g/rat/week) and fluid intake (ml/rat/week) were recorded. Fasting blood glucose levels were measured using a glucometer. Serum and hypothalamic levels of triglycerides, cholesterol, glucose, leptin, SOCS3, Obrb, TNF-α, and IL-6 were determined by ELISA. Results: In the fructose-fed group (F), hypothalamic triglyceride, TNF-α, IL-6, leptin, and SOCS3 levels were significantly increased, while Obrb levels were decreased compared to the C group (p < 0,01). CA and/or IF treatments ameliorated these alterations. Especially, in the F+CA+IF group, a significant reduction in leptin and SOCS3 levels and a marked increase in Obrb levels were observed (p < 0,001). Although favorable effects were also observed in some parameters in the groups in which KA and IF were administered separately, it was observed that the combined application provided a stronger corrective effect. Conclusion: Chronic high fructose intake induces both peripheral and central inflammation and impairs hypothalamic leptin signaling. The upregulation of SOCS3 and down regulation of Obrb indicate the development of leptin resistance. CA and IF, particularly when used in combination, alleviate fructose-induced inflammatory and neurometabolic disturbances by modulating the leptin-SOCS3-Obrb axis.