Dipesh Bhakta

Introduction. Hypertension is a silent, chronic disease that leads to severe health complications such as heart disease and stroke, which are the leading causes of death in the United States¹.75 million American adults (33%) have hypertension. This increases to 60% for adults over 60, and more than 75% for adults greater than 70¹. Studies have determined high saturated fat diets trigger inflammation of the arcuate nucleus (ARC) of the hypothalamus, which is responsible for regulation of energy intake and expenditure^1-6. Inflammatory insults act in the hypothalamus to induce central ER stress, and activate the hypothalamic proinflammatory IKKβ/NF-κB pathway^2,3. Unsaturated fatty acids have been shown to inhibit hypothalamic proinflammatory pathways while activating hypothalamic anti-inflammatory pathways. Thus, they are promising treatment therapies for diet induced hypertension⁴. Methods. In mice models on High Fat Diets (HFD), expressions of inflammatory markers (iNOS,IL-6, TNF-α, pJNK), anti-inflammatory cytokines (IL-10), proapoptotic proteins (Bax), and antiapoptotic proteins (Bcl-2) in hypothalami were measured via immunoblotting and inflorescence. Expression of these markers were compared at the end of a 7-day period between the control mice (which were treated with a diluent (albumin)) and the experimental mice (which were treated with ω3 or ω9 unsaturated fatty acid). Results. Mice with diets high in unsaturated fatty acids had significant reduction in the hypothalamic inflammatory markers iNOS, IL-6, TNF-α, and pJNK³.Also, hypothalamic expression of the anti-inflammatory cytokine, IL-10 was significantly increased². Additionally, there was a reduction in pro-apoptotic protein, Bax, and an increase in the expression of the anti-apoptotic protein, Bcl-2 ³. Unsaturated fatty acids can activate the anti-inflammatory effects of TLR4 or TNF-α inhibition, as well as directly reduce concentrations of inflammatory cytokines. Conclusions. Studies have shown high saturated fat diets induce inflammation of the hypothalamic nucleus. This inflammation disrupts metabolic homeostasis and is associated with hypertension via increased sympathetic activity from the hypothalamic proinflammatory IKKβ/NF-κB pathway^2,3,4. Saturated fatty acids (ω3 and ω9) have been shown to downregulate inflammatory pathways of the ARC, as well as upregulate anti-inflammatory pathways of the ARC. Unsaturated fatty acids can activate the anti-inflammatory effects of TNF-α inhibition, directly reduce concentrations of inflammatory cytokines and directly increase the concentrations of anti-inflammatory cytokines. Thus, unsaturated fatty acids may contribute to protecting against diet induced hypertension and inflammation of the hypothalamus.

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