Over the past decades, obesity rates have continued to increase at alarming rates globally, fostering the rise in serious comorbidities, particularly cardiovascular diseases and type 2 diabetes, collectively known as metabolic syndrome (MetS). Obesity is also linked with brain disease and is often associated with a high prevalence of mood and cognitive disorders that emerge as additional risk factors for obesity-related systemic pathological complications. Understanding the etiology of these disorders therefore represents a major public health challenge. In the present chapter, we aim to provide a new perspective on the pathophysiological mechanisms contributing to the development of these disorders. On the basis of recent experimental data obtained by using animal models of obesity/MetS, we propose that these disorders may reflect the neural consequences of molecular and cellular events playing a pivotal role in obesity and more importantly that inflammation/neuroinflammation, which is one of the key components of obesity/MetS, may contribute to the development of these behavioral alterations. We indeed provide converging evidence showing that brain dysfunctions related with neuroinflammation, particularly when they occur in key brain areas for mood, learning, and memory such as the hippocampus contribute to impair mood and cognition in models of obesity/MetS. These findings may prove valuable for introducing new strategies to treat neuropsychiatric complications reported in chronically obese/MetS patients.< Réduire