Unraveling the “metabolic syndrome and cognitive decline” detrimental loop: What role for Mediterranean phytonutrients?

Metabolic Syndrome (MetS) and obesity correlate with cognitive impairment, heightening the susceptibility to cognitive decline and dementia. Noteworthy, cognitive impairment exacerbates weight management challenges in MetS, giving rise to a "cognitive decline-MetS" loop. Indeed, various cognitive and affective functions, including memory and executive functions, were found to be compromised in MetS, with underlying mechanistic pathways supporting a potential role of oxy-inflammatory signaling.Our research delves into the nuanced realm of cognitive alterations in MetS by examining the correlation of multi-dimensional biomarkers and the protective influence of specific Mediterranean Phytonutrients (MediPhy) in a high-fat diet (HFD) rat model. We explored multi-faceted parameters unraveling behavioral, molecular, cognitive, and dysmetabolic alterations. Our cross-correlation analyses enlighten specific trajectories offering insights akin to widely recognized MetS biomarkers.The interventions carried out in our study, administering MediPhy from sources like "golden" tomato and Opuntia Ficus Indica, exhibit promise in modulating neural function, potentially due to concurrent amelioration of systemic dysmetabolism, redox homeostasis, and leptin resistance. Nutritional supplementation with MediPhy for one month demonstrates notable enhancements in behavioral reactivity, anxiety, anhedonia, and declarative memory in rats with MetS-associated cognitive alterations. At the molecular level, MediPhy supplementation could counteract HFD-induced neuroinflammatory signaling pathways such as mitogen‑activated protein kinase (MAPK)/Extracellular signal-regulated kinase (Erk) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) in regions like prefrontal cortex, hippocampus, and hypothalamus.Collectively, these findings emphasize the crucial role of functional food supplementation in ameliorating central oxy-inflammation and cognitive profile associated with MetS, tracing paths for developing effective prevention approaches.