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Dietary Fats: Beneficial or Detrimental for Lifestyle-Related Diseases?

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Lipids".

Deadline for manuscript submissions: 5 June 2025 | Viewed by 2212

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Guest Editor
Departments of Cell Metabolism and Nutrition, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
Interests: Alzheimer’s disease; hydroxynonenal; vegetable oils; type 2 diabetes; nonalcoholic steatohepatitis; cell death; diet
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Special Issue Information

Dear Colleagues,

Currently, lifestyle-related diseases such as Alzheimer’s disease, type 2 diabetes, chronic heart, liver, and kidney diseases, among others, constitute increasingly prevalent life-threatening diseases. However, the causal relationship and cross-talk between each disease remain poorly understood. The pathophysiologies of the diseases are complex, multi-faceted, and multi-angled. Oxidative stress due to the prolonged generation of reactive oxygen species (ROS) induces mitochondrial dysfunction, endoplasmic reticulum stress, lysosomal disintegrity, impaired autophagy, etc., in human organs. The characteristics of lifestyle-related diseases include progressive loss of function due to cell degeneration/death in various tissues and organs. ROS-induced lipid and protein oxidation synergically play crucial roles in the development of cell degeneration and death. For example, high-fat diets containing saturated fatty acids like palmitate are known to be associated with an increase in the cellular ROS level because excessive β-oxidation induces stress in mitochondria and peroxisomes. In addition, deep-fried foods cooked in ω-6 polyunsaturated fatty acid-rich vegetable oils, such as rapeseed (canola), soybean, sunflower, and corn oils, already contain or intrinsically generate highly reactive aldehydes such as “4-hydroxy-2-nonenal” through peroxidation. Cooking oils have a close relationship with each other in both health and diseases. The excessive consumption of deep-fried foods is regarded as one of the most important epidemiological factors driving lifestyle-related diseases. By considering the beneficial and detrimental aspects of fatty acids involved in food oils, this Special Issue will accelerate the rational development of preventive, disease-modifying, and symptomatic treatments for lifestyle-related diseases.

Dr. Tetsumori Yamashima
Guest Editor

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Keywords

  • lifestyle-related disease
  • palmitic acid
  • PUFA
  • ROS
  • cell degeneration/death
  • hydroxynonenal
  • cooking oil
  • deep-fried food
  • mitochondria
  • lysosome
  • high-fat diets

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Published Papers (1 paper)

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Review

26 pages, 10074 KiB  
Review
4-Hydroxynonenal from Mitochondrial and Dietary Sources Causes Lysosomal Cell Death for Lifestyle-Related Diseases
by Tetsumori Yamashima
Nutrients 2024, 16(23), 4171; https://doi.org/10.3390/nu16234171 - 30 Nov 2024
Cited by 2 | Viewed by 1866
Abstract
Excessive consumption of vegetable oils such as soybean and canolla oils containing ω-6 polyunsaturated fatty acids is considered one of the most important epidemiological factors leading to the progression of lifestyle-related diseases. However, the underlying mechanism of vegetable-oil-induced organ damage is incompletely elucidated. [...] Read more.
Excessive consumption of vegetable oils such as soybean and canolla oils containing ω-6 polyunsaturated fatty acids is considered one of the most important epidemiological factors leading to the progression of lifestyle-related diseases. However, the underlying mechanism of vegetable-oil-induced organ damage is incompletely elucidated. Since proopiomelanocortin (POMC) neurons in the hypothalamus are related to the control of appetite and energy expenditure, their cell degeneration/death is crucial for the occurrence of obesity. In patients with metabolic syndrome, saturated fatty acids, especially palmitate, are used as an energy source. Since abundant reactive oxygen species are produced during β-oxidation of the palmitate in mitochondria, an increased amount of 4-hydroxy-2-nonenal (4-HNE) is endogenously generated from linoleic acids constituting cardiolipin of the inner membranes. Further, due to the daily intake of deep-fried foods and/or high-fat diets cooked using vegetable oils, exogenous 4-HNE being generated via lipid peroxidation during heating is incorporated into the blood. By binding with atheromatous and/or senile plaques, 4-HNE inactivates proteins via forming hybrid covalent chemical addition compounds and causes cellular dysfunction and tissue damage by the specific oxidation carbonylation. 4-HNE overstimulates G-protein-coupled receptors to induce abnormal Ca2+ mobilization and µ-calpain activation. This endogenous and exogenous 4-HNE synergically causes POMC neuronal degeneration/death and obesity. Then, the resultant metabolic disorder facilitates degeneration/death of hippocampal neurons, pancreatic β-cells, and hepatocytes. Hsp70.1 is a molecular chaperone which is crucial for both protein quality control and the stabilization of lysosomal limiting membranes. Focusing on the monkey hippocampus after ischemia, previously we formulated the ‘calpain–cathepsin hypothesis’, i.e., that calpain-mediated cleavage of carbonylated Hsp70.1 is a trigger of programmed neuronal death. This review aims to report that in diverse organs, lysosomal cell degeneration/death occurs via the calpain–cathepsin cascade after the consecutive injections of synthetic 4-HNE in monkeys. Presumably, 4-HNE is a root substance of lysosomal cell death for lifestyle-related diseases. Full article
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