Intake of ω-6 Polyunsaturated Fatty Acid-Rich Vegetable Oils and Risk of Lifestyle Diseases

Abstract

<jats:title>Abstract</jats:title> <jats:p>Although excessive consumption of deep-fried foods is regarded as 1 of the most important epidemiological factors of lifestyle diseases such as Alzheimer's disease, type 2 diabetes, and obesity, the exact mechanism remains unknown. This review aims to discuss whether heated cooking oil-derived peroxidation products cause cell degeneration/death for the occurrence of lifestyle diseases. Deep-fried foods cooked in ω-6 PUFA-rich vegetable oils such as rapeseed (canola), soybean, sunflower, and corn oils, already contain or intrinsically generate “hydroxynonenal” by peroxidation. As demonstrated previously, hydroxynonenal promotes carbonylation of heat-shock protein 70.1 (Hsp70.1), with the resultant impaired ability of cells to recycle damaged proteins and stabilize the lysosomal membrane. Until now, the implication of lysosomal/autophagy failure due to the daily consumption of ω-6 PUFA-rich vegetable oils in the progression of cell degeneration/death has not been reported. Since the “calpain-cathepsin hypothesis” was formulated as a cause of ischemic neuronal death in 1998, its relevance to Alzheimer's neuronal death has been suggested with particular attention to hydroxynonenal. However, its relevance to cell death of the hypothalamus, liver, and pancreas, especially related to appetite/energy control, is unknown. The hypothalamus senses information from both adipocyte-derived leptin and circulating free fatty acids. Concentrations of circulating fatty acid and its oxidized form, especially hydroxynonenal, are increased in obese and/or aged subjects. As overactivation of the fatty acid receptor G-protein coupled receptor 40 (GPR40) in response to excessive or oxidized fatty acids in these subjects may lead to the disruption of Ca2+ homeostasis, it should be evaluated whether GPR40 overactivation contributes to diverse cell death. Here, we describe the molecular implication of ω-6 PUFA-rich vegetable oil-derived hydroxynonenal in lysosomal destabilization leading to cell death. By oxidizing Hsp70.1, both the dietary PUFA- (exogenous) and the membrane phospholipid- (intrinsic) peroxidation product “hydroxynonenal,” when combined, may play crucial roles in the occurrence of diverse lifestyle diseases including Alzheimer's disease.</jats:p>

Hydroxynonenal causes Langerhans cell degeneration in the pancreas of Japanese macaque monkeys

“…5, 6b). Hydroxynonenal is generated as a consequence of H 2 O 2 -mediated lipid peroxidation of biomembranes composing of ω-6 polyunsaturated fatty acids such as linoleic and arachidonic acid [11,59,60]. Therefore, it is reasonable to speculate that exogenous hydroxynonenal is a causative substance and also a trigger, which induce consecutive peroxisomal HO • production with the resultant intrinsic hydroxynonenal generation in the monkey pancreas (Fig.…”

“…8). By inducing Hsp70.1 disorder, hydroxynonenal conceivably plays sinister roles in the occurrence of diverse lifestyle diseases [11].…”

“…β-cells exposed to oxidative, excessive or conjugated NEFAs develop cell degeneration/death [3,4,5]. The molecular mechanisms underlying the oxidative injury due to ROS, comprise of endoplasmic reticulum (ER) stress, mitochondrial dysfunction, impaired autophagy, lysosomal disintegrity, inflammation, and mixture of them [6,7,8,9,10,11]. These molecular events are grossly similar to the neurodegeneration of hypothalamic arcuate nucleus occurring after the intake of high-fat diets [12] or hippocampal CA1 sector exposed to the oxidative stress during reperfusion after transient ischemia [3].…”

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

“…However, additional risk factors for vascular dementia include hypertension, low education in early life, alcohol consumption, and tobacco use that can limit treatment efficacy [3,22,31,[59][60][61]. In regard to metabolic disorders, early diagnosis and treatment of DM may offer some degree of protection to inhibit disease progression, but tight serum glucose control cannot completely prevent the complications from DM [5,8,16,[62][63][64][65][66][67][68][69][70][71]. In light of the present challenges to overcome cognitive loss, innovative therapeutic strategies are necessary to develop new treatments for dementia.…”

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

“…Yet, there exist other risks for developing vascular cognitive loss that can affect the efficacy of treatments such as tobacco use, alcohol consumption, hypertension, and a low level of education [20,39,[54][55][56][57]. With reference to metabolic disease, tight glucose control in the serum in combination with early diagnosis of DM may assist to limit the progression of the disease, but complications from DM can still ensue [6,[58][59][60][61][62][63][64][65][66][67][68][69]. Given the need for novel strategies directed against memory loss and dementia, exciting new avenues of development are now focusing upon biological clock mechanisms and include the pathways of the mechanistic target of rapamycin (mTOR), its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), the growth factor erythropoietin (EPO), and the wingless pathway of Wnt pathway (Fig.…”