LIRAGLUTIDE IMPROVES SPATIAL LEARNING AND MEMORY IN OBESE RATS: POSSIBLE INVOLVEMENT OF HIPPOCAMPAL NEUROINFLAMMATION AND NITRIC OXIDE SIGNALING

This study investigated the effects of liraglutide and a low-fat diet on spatial learning and memory in obese rats, with a particular focus on hippocampal neuroinflammation and nitric oxide–related mechanisms.
Obesity was induced by feeding rats a high-fat diet (40% carbohydrates, 25% protein, and 35% fat) for six weeks. Rats with a Lee obesity index greater than 315 were classified as obese. Following obesity induction, rats were assigned to five groups: (1) Control (C, standard diet), (2) Obese (O, continued high-fat diet), (3) Obese + low-fat diet (OLF, 72% carbohydrates, 24% protein and 4% fat), (4) Obese + liraglutide (OLI; Saxenda® ( 6mg/ml), 0.3 mg/kg/day, intraperitoneally), and (5) Combination therapy (COM; low-fat diet + liraglutide). Treatments were administered for three weeks.
Spatial learning and memory were evaluated using the Barnes maze test. Hippocampal TNF-alpha (TNF-α) levels were measured as an index of neuroinflammation, while nitric oxide (NO) levels were assessed as an indicator of altered nitric oxide signaling.
Obese rats exhibited significant impairments in spatial learning and memory compared to controls. In contrast, all treatment groups demonstrated marked improvements in cognitive performance. These behavioral benefits were accompanied by significant reductions in hippocampal TNF-α and NO levels.
In conclusion, liraglutide ameliorates obesity-associated deficits in spatial learning and memory, at least in part, through modulation of hippocampal neuroinflammation and nitric oxide signaling. These findings suggest a potential neuroprotective role of GLP-1 receptor agonists in obesity-related cognitive dysfunction.