Neurochemical Effects of Long Term Consumption of High Fat Diet

Abstract

Long term consumption of high fat diet induces alterations in hypothalamus and hippocampal signaling leading to neuroinflammation and oxidative stress. High fat diet-mediated alterations in hypothalamus and hippocampal signaling involve ER stress and mitochondrial dysfunctions, and insulin resistance. Several mechanisms may contribute to high fat diet-mediated inflammation in hypothalamus and peripheral tissues. These mechanisms include the activation of TLR4 receptors, induction of ER stress, and activation of IKKβ. The relative contribution of these mechanisms in the induction of hypothalamic and peripheral inflammation remains unknown. However, early onset of inflammation in the hypothalamus relative to that in peripheral tissues suggests that different processes may cause inflammation in the peripheral tissues and hypothalamus. At the molecular level, inflammation is not only supported by elevation in levels of ARA and its lipid mediators (PGs, LTs, and TXs) and increase in platelet activating factor, but also with increase in expression of proinflammatory genes including genes for cytokines (TNF-α, IL-1β, and IL-6) along with activation of proinflammatory enzymes (secretory phospholipase A2, cyclooxygenase-2, and nitric oxide synthase). High fat diet is a major cause of obesity which is closely linked to a variety of health issues, including coronary heart disease, stroke, high blood pressure, fatty liver disease, diabetes, certain cancers, and neurological disorders. The consumption of high fat diet not only produces free radicals, but also contributes to the development of systemic inflammation and insulin resistance through the involvement of lipid-sense nuclear factors such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors, which play critical roles in cellular fatty acid and carbohydrate metabolism as well as cell proliferation. High fat-mediated changes in hippocampus have negative impact on cognitive function not only due to vascular defects and impaired insulin metabolism, but also due to the defect in glucose transport mechanisms in brain.