Dissociation between metabolic and neurobehavioral effects of metformin in a model of chronic fructose consumption in female mice

Abstract

Excessive fructose intake is increasingly recognized as a contributor to metabolic dysfunction and associated neurobehavioral disturbances, including pain and emotional alterations. This study investigated whether metformin could mitigate the metabolic, nociceptive, and emotional impairments induced by chronic fructose consumption in female Swiss mice. Animals received a 30% fructose solution in their drinking water for 14 weeks, and a subset was treated with metformin (4 mg/mL in the drinking solution) during the final four weeks. Fructose-fed mice developed marked metabolic dysfunction, characterized by fasting hyperglycemia, glucose intolerance, and increased plasma cholesterol, accompanied by mechanical allodynia, cold allodynia and cold hyperalgesia, and depressive- and anxiety-like behaviors. Metformin treatment effectively improved glycemic control but failed to reverse nociceptive hypersensitivity or emotional disturbances. These findings indicate that, under the present experimental conditions, metabolic improvement induced by metformin was not accompanied by detectable improvement in neurobehavioral outcomes.