Behavioral, neuroanatomic, and neuroinflammatory characteristics of metabolic syndrome in cafeteria diet-induced obese male rats.

Obesity and metabolic syndrome are associated with low-grade systemic inflammation and neuroinflammation, potentially contributing to structural brain alterations and cognitive decline. This study evaluated brain volumetry, metabolic disturbances, neuroinflammation markers, and behavioral outcomes in a rat model of diet-induced obesity. Male Wistar rats were fed either a standard diet (CTRL; n = 6) or a cafeteria diet (CAF; n = 6) for five months from weaning. Metabolic parameters (weight, glucose tolerance, blood pressure, lipids), behavior (Open Field, Novel Object Recognition), and brain regional volumes (4.7 T MRI) were assessed. Neuroinflammatory markers (tumor necrosis factor-α levels (TNF-α) and glial fibrillary acidic protein (GFAP)) were quantified in the hypothalamus and olfactory bulb. CAF rats developed a metabolic syndrome-like phenotype characterized by abdominal adiposity, insulin resistance, hypertension, and dyslipidemia (p < 0.05). They also showed higher hypothalamic GFAP and TNF-α levels, higher relative orbitofrontal cortex volume (p < 0.05) than controls, whereas lower relative hypothalamic and corpus callosum volumes did not reach significance. Behaviorally, CAF rats exhibited reduced locomotor activity, impaired short-term memory, and higher grooming activity (p < 0.05). Multivariate modeling identified hypothalamic neuroinflammation, severity of continuous metabolic syndrome z-score, and reduced corpus callosum volume as key predictors of cognitive and behavioral impairments. Long-term consumption of a CAF diet induces key features of human metabolic syndrome, hypothalamic neuroinflammation, region-specific brain volumetric alterations, and cognitive deficits. These findings support a role for the metabolic-inflammatory axis in brain vulnerability and suggest that preservation of neuroimmune homeostasis may be important for maintaining cognitive health in obesity-associated metabolic disorders.