OBESITY, EMOTIONNALITY AND NEUROINFLAMATION: EXPLORING THE EFFECTS OF THE FAT-TASTE ENHANCER NKS-3 AS A POTENTIAL PREVENTIVE TREATMENT

Obesity is a complex chronic disease associated with the emergence of metabolic, cardiovascular and neuropsychiatric comorbidities. It is characterized by a dysregulation of brain circuits involved in energy homeostasis, food reward and cognitive control, in close interaction with peripheral signals. Obesity has been associated with the alteration of multiple neurobiological substrates, including the brain derived neurotrophic factor (BDNF), which can be restored with physical exercise, fasting or both.
In the search for new therapeutic strategies to treat this multifactorial pathology, we use the non-caloric fat-taste enhancer NKS-3 as a pharmacological tool able to in vivo modulate fat-taste perception and signalling. NKS-3 is a high-affinity agonist for the lingual CD36 taste receptor, which expression is known to be down-regulated in individuals suffering from obesity. In recent preclinical studies, we showed that NKS-3 reduces weight-gain in male mice fed a high-fat diet (HFD), and has general systemic and central anti-inflammatory properties. Moreover, our preliminary results suggest a potential effect of NKS-3 upon behavioural aspects, improving the altered emotionality observed in HFD untreated individuals. Our data also suggest that NKS-3 exerts its properties via a metabolic enhancer’s effect not yet described. Aiming at elucidating the underlying mechanisms of these NKS-3 effects, we here propose to investigate the existence of a potential synergy of NKS-3 with physical activity, and with intermittent fasting upon emotionality and metabolism. Neurobiological aspects such as cortical and hippocampal BDNF expression and central pro-inflammatory cytokines levels are also to be explored.