Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity

Hosoi, Toru; Kuwamura, Ayaka; Thon, Mina; Tsuchio, Kyoji; El-Hafeez, Amer Ali Abd; Ozawa, Koichiro

doi:10.1152/ajpcell.00080.2018

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…An aldehyde, 4-hydroxy-2-nonenal (4-HNE), may be involved in the development of leptin resistance in neuronal cells. Levels of this aldehyde can rise with fat accumulation which can initiate an ER stress response and further increase its production, and can then lead to impaired leptin signalling and obesity [94]. The elevated free fatty acid concentration in the hypothalamus can lead to lipotoxicity.…”

Section: Hypothalamic Endoplasmic Reticulum Stress and Leptin Resistancementioning

confidence: 99%

Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin

Flores-Cordero

Pérez-Pérez

Jiménez‐Cortegana

et al. 2022

IJMS

112

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Obesity is a growing worldwide health problem, affecting many people due to excessive saturated fat consumption, lack of exercise, or a sedentary lifestyle. Leptin is an adipokine secreted by adipose tissue that increases in obesity and has central actions not only at the hypothalamic level but also in other regions and nuclei of the central nervous system (CNS) such as the cerebral cortex and hippocampus. These regions express the long form of leptin receptor LepRb, which is the unique leptin receptor capable of transmitting complete leptin signaling, and are the first regions to be affected by chronic neurocognitive deficits, such as mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). In this review, we discuss different leptin resistance mechanisms that could be implicated in increasing the risk of developing AD, as leptin resistance is frequently associated with obesity, which is a chronic low-grade inflammatory state, and obesity is considered a risk factor for AD. Key players of leptin resistance are SOCS3, PTP1B, and TCPTP whose signalling is related to inflammation and could be worsened in AD. However, some data are controversial, and it is necessary to further investigate the underlying mechanisms of the AD-causing pathological processes and how altered leptin signalling affects such processes.

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Section: Hypothalamic Endoplasmic Reticulum Stress and Leptin Resistancementioning

confidence: 99%

Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin

Flores-Cordero

Pérez-Pérez

Jiménez‐Cortegana

et al. 2022

IJMS

112

View full text Add to dashboard Cite

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“…It is known that anti-obesity hormone leptin signaling as well as insulin signaling mediate the regulation of PPARα. Insulin resistance is improved by 4-HNE [96], which also selectively inhibits leptin signaling, possibly promoting the pathogenesis of leptin resistance in obesity [134]. Some medicinal plants and natural compounds acting on PPARα, leptin, or insulin signaling may be responsible for the therapeutic effects on 4-HNE-induced energy metabolism disorders [85].…”

Section: The Strategy For Developing Potential Therapymentioning

confidence: 99%

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

Wang

et al. 2020

Biomolecules

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The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.

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Aldose reductase and protein tyrosine phosphatase 1B inhibitors as a promising therapeutic approach for diabetes mellitus

Kousaxidis

Petrou

Lavrentaki

et al. 2020

European Journal of Medicinal Chemistry

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Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity

Cited by 4 publications

References 56 publications

Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin

Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

Aldose reductase and protein tyrosine phosphatase 1B inhibitors as a promising therapeutic approach for diabetes mellitus

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