The prevalence of metabolic syndrome caused by diets containing excessive fatty acids is increasing worldwide. Patients with metabolic syndrome exhibit abnormal lipid profiles, chronic inflammation, increased levels of saturated fatty acids, impaired insulin sensitivity, excessive fat accumulation, and neuropathological issues such as memory deficits. In particular, palmitic acid (PA) in saturated fatty acids aggravates inflammation, insulin resistance, impaired glucose tolerance, and synaptic failure. Recently, adiponectin, brainderived neurotrophic factor (BDNF), and glucose-like peptide-1 (GLP-1) have been investigated to find therapeutic solutions for metabolic syndrome, with findings suggesting that they are involved in insulin sensitivity, enhanced lipid profiles, increased neuronal survival, and improved synaptic plasticity. We investigated the effects of adiponectin, BDNF, and GLP-1 on neurite outgrowth, length, and complexity in PA?treated primary cortical neurons using Sholl analysis. Our findings demonstrate the therapeutic potential of adiponectin, BDNF, and GLP-1 in enhancing synaptic plasticity within brains affected by metabolic imbalance. We underscore the need for additional research into the mechanisms by which adiponectin, BDNF, and GLP-1 influence neural comp...