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Nutrients and the Risk of Lifestyle-Related Diseases

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

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 2801

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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,

Alzheimer’s disease (AD), type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) are chronic health disorders that currently affect millions of people around the world. The risk for developing these diseases increases exponentially with age because of the reduction in anti-oxidation enzymes, so each disease has a close relation with each other. For example, patients with T2DM have an increased risk of developing AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and ω-3 fatty acid-rich polyunsaturated fatty acids is beneficial to preventing lifestyle-related disease, and consumption of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduces the risk. During the last four decades, lipid peroxidation products have been shown to be involved in a great number of pathologies, such as metabolic diseases, neurodegenerative diseases, and cancers. In particular, elevation of the ω-6 fatty acid oxidation product ‘hydroxynonenal’ in serum and various organs was recently reported to be responsible for the occurrence of organ damage in both experimental animals and humans. However, the precise role of hydroxynonenal in each disease or in the disease interaction is not well understood. Since Hsp70.1 has dual functions as a molecular chaperone and lysosomal stabilizer, hydroxynonenal conceivably has a crucial impact on cell death fate by the oxidation of Hsp70.1. It is probable that the dietary ω-6 fatty acid (exogenous; from cooking oils, deep-fried foods, etc.) and the biomembrane phospholipid (intrinsic; associated with electromagnetic waves, air pollution, etc.) peroxidation product hydroxynonenal plays crucial roles in lysosomal cell death in the brain, pancreas, and liver, via oxidation of diverse house-keeping proteins, including Hsp70.1. It is likely that these lifestyle-related diseases might occur in response to the exogenous and intrinsic hydroxynonenal, causing long-standing cell degeneration/death in the corresponding organ. The Special Issue aims at elucidating the common mechanism or causative factor of AD, T2DM and/or NASH, particularly focusing on the detrimental effects of nutrients, especially ω-6 fatty acids.

Dr. Tetsumori Yamashima
Guest Editor

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Research

23 pages, 18610 KiB  
Article
Vegetable Oil-Peroxidation Product ‘Hydroxynonenal’ Causes Hepatocyte Injury and Steatosis via Hsp70.1 and BHMT Disorders in the Monkey Liver
by Tetsumori Yamashima, Yurie Mori, Takuya Seike, Sharif Ahmed, Piyakarn Boontem, Shihui Li, Shinji Oikawa, Hatasu Kobayashi, Tatsuya Yamashita, Mitsuru Kikuchi, Shuichi Kaneko and Eishiro Mizukoshi
Nutrients 2023, 15(8), 1904; https://doi.org/10.3390/nu15081904 - 14 Apr 2023
Cited by 1 | Viewed by 2406
Abstract
Hsp70.1 has a dual function as a chaperone protein and lysosomal stabilizer. In 2009, we reported that calpain-mediated cleavage of carbonylated Hsp70.1 causes neuronal death by inducing lysosomal rupture in the hippocampal CA1 neurons of monkeys after transient brain ischemia. Recently, we also [...] Read more.
Hsp70.1 has a dual function as a chaperone protein and lysosomal stabilizer. In 2009, we reported that calpain-mediated cleavage of carbonylated Hsp70.1 causes neuronal death by inducing lysosomal rupture in the hippocampal CA1 neurons of monkeys after transient brain ischemia. Recently, we also reported that consecutive injections of the vegetable oil-peroxidation product ‘hydroxynonenal’ induce hepatocyte death via a similar cascade in monkeys. As Hsp70.1 is also related to fatty acid β-oxidation in the liver, its deficiency causes fat accumulation. The genetic deletion of betaine-homocysteine S-methyltransferase (BHMT) was reported to perturb choline metabolism, inducing a decrease in phosphatidylcholine and resulting in hepatic steatosis. Here, focusing on Hsp70.1 and BHMT disorders, we studied the mechanisms of hepatocyte degeneration and steatosis. Monkey liver tissues with and without hydroxynonenal injections were compared using proteomics, immunoblotting, immunohistochemical, and electron microscopy-based analyses. Western blotting showed that neither Hsp70.1 nor BHMT were upregulated, but an increased cleavage was observed in both. Proteomics showed a marked downregulation of Hsp70.1, albeit a two-fold increase in the carbonylated BHMT. Hsp70.1 carbonylation was negligible, in contrast to the ischemic hippocampus, which was associated with ~10-fold increments. Although histologically, the control liver showed very little lipid deposition, numerous tiny lipid droplets were seen within and around the degenerating/dying hepatocytes in monkeys after the hydroxynonenal injections. Electron microscopy showed permeabilization/rupture of lysosomal membranes, dissolution of the mitochondria and rough ER membranes, and proliferation of abnormal peroxisomes. It is probable that the disruption of the rough ER caused impaired synthesis of the Hsp70.1 and BHMT proteins, while impairment of the mitochondria and peroxisomes contributed to the sustained generation of reactive oxygen species. In addition, hydroxynonenal-induced disorders facilitated degeneration and steatosis in the hepatocytes. Full article
(This article belongs to the Special Issue Nutrients and the Risk of Lifestyle-Related Diseases)
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