Chronic Caffeine Consumption Prevents Body Weight Gain and Glucose Intolerance in High-Fat Diet-Induced Obesity Mice Model

Background/Objectives: Caffeine consumption has been reported to have beneficial effects in metabolic disorders; however, its effects on food intake are not fully elucidated. This study evaluated the impact of chronic caffeine consumption on weight gain, food intake, and metabolic parameters in C57BL/6 male mice. Methods: Eight-week-old male mice (28 animals) were divided into four groups: control (chow diet), caffeine (chow diet + 1 g/L caffeine in drinking water), high-fat diet (HFD), and HFD + caffeine (HFD + 1 g/L caffeine in drinking water). Diets and caffeine were provided ad libitum for 8 weeks. Food and water intake were recorded weekly, and blood glucose was measured every 4 weeks. After 8 weeks of diet and caffeine exposure, metabolic tests were conducted, and tissues were collected for biochemical analysis. Results: HFD consumption for 8 weeks induced an increase in body weight and adiposity compared to the chow diet, without changes in food intake. Caffeine consumption prevented body weight gain and adiposity, although it increased food intake. Caffeine also improved glucose tolerance in the HFD mouse model, without changes in random blood glucose, triglyceride, or cholesterol levels. Analysis of hypothalamic neuropeptide (Agrp, NPY, Pomc, Cart), involved in the control of food intake, showed no differences in expression. There were also no changes observed in locomotion nor in anxiety-like behavior. Conclusions: In conclusion, chronic high-fat diet (HFD) exposure induced obesity characterized by increased body weight and adiposity without altering food intake. Chronic caffeine consumption counteracted HFD-induced weight gain and fat accumulation and improved glucose tolerance, despite increasing food intake. Importantly, caffeine consumption in the HFD group did not affect locomotor activity or anxiety-like behavior, suggesting that its metabolic effects are not driven by changes in general activity or emotional state. Overall, these findings indicate that chronic caffeine consumption improves metabolic homeostasis in HFD-fed mice.