Unsaturated Fatty Acids Revert Diet-Induced Hypothalamic Inflammation in Obesity

Background: In experimental models, hypothalamic inflammation is an early and determining factor in the installation and progression of obesity. Pharmacological and gene-based approaches have proven efficient in restraining inflammation and correcting the obese phenotypes. However, the role of nutrients in the modulation of hypothalamic inflammation is unknown. Methodology/Principal Findings: Here we show that, in a mouse model of diet-induced obesity, partial substitution of the fatty acid component of the diet by flax seed oil (rich in C18:3) or olive oil (rich in C18:1) corrects hypothalamic inflammation, hypothalamic and whole body insulin resistance, and body adiposity. In addition, upon icv injection in obese rats, both omega 3 and omega 9 pure fatty acids reduce spontaneous food intake and body mass gain. These effects are accompanied by the reversal of functional and molecular hypothalamic resistance to leptin/insulin and increased POMC and CART expressions. In addition, both, omega 3 and omega 9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of omega 3 and omega 9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor. Conclusions/Significance: Unsaturated fatty acids can act either as nutrients or directly in the hypothalamus, reverting diet-induced inflammation and reducing body adiposity. These data show that, in addition to pharmacological and genetic approaches, nutrients can also be attractive candidates for controlling hypothalamic inflammation in obesity.