Unsaturated Fatty Acids Revert Diet-Induced Hypothalamic Inflammation in Obesity

Abstract

BackgroundIn 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 FindingsHere 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 ω3 and ω9 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, ω3 and ω9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of ω3 and ω9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor.Conclusions/SignificanceUnsaturated 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.

MECHANISMS IN ENDOCRINOLOGY: Hypothalamic inflammation and nutrition

“…PUFAs can also attenuate hypothalamic inflammation in animal models of obesity (78). In diet-induced obesity, the dietary substitution of lard with either flaxseed or olive oil resulted in reduced caloric intake and reduced body mass gain (78).…”

Chiropractic Management of a Patient With Chronic Fatigue: A Case Report

“…31 Eicosapentaenoic acid and DHA have a specific reversion effect on hypothalamic inflammation, which may aid in the function of the HPA axis, especially in overweight individuals. 32 Ascorbate has been seen to be a functional cofactor for both the adrenal cortex and the medulla in the production of cortisol, DHEA, epinephrine, and norepinephrine. 33 To have physiologic effects on the HPA axis, including the brain and the adrenal glands, and also to treat a patient with inflammation, as described in this case study, therapeutic dosages of 3 g ascorbate have been used with limited side effects.…”

Rôle de la détection centrale des lipides dans le contrôle nerveux de la balance énergétique

“…Un régime riche en lipides induit chez le rat une augmentation du turnover des monoamines [42] et de l'activité nerveuse sympathique. Enfin, un lien entre surcharge central en lipides et dysfonctionnement des activités neuronales peut être l'apparition d'une inflammation, comme cela a été récemment montré [43]. Parmi les métabolites des acides gras potentiellement délétères, on peut aussi mentionner les céramides [9].…”