Redox status, inflammation, necroptosis and inflammasome as indispensable contributors to high fat diet (HFD)-induced neurodegeneration; Effect of N-acetylcysteine (NAC)

Keshk, Walaa Arafa; Ibrahim, Marwa A.; Shalaby, Shahinaz M.; Zalat, Zeinab; Elseady, Walaa S.

doi:10.1016/j.abb.2019.108227

Cited by 24 publications

(12 citation statements)

References 43 publications

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“…It is now widely accepted that the consumption of HFD is a risk factor for the development of obesity-related diseases and prolonged HFD feeding has been reported to accelerate the pathogenesis of neurodegeneration [5,28,29], leading to impairment of cognitive functions in rodents [29].…”

Section: Discussionmentioning

confidence: 99%

Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice

et al. 2020

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Obesity has been associated with neurodegeneration and cognitive dysfunctions. Recent data showed that pistachio consumption is able to prevent and ameliorate dyslipidemia, hepatic steatosis, systemic and adipose tissue inflammation in mice fed a high-fat diet (HFD). The present study investigated the neuroprotective effects of pistachio intake in HFD mice. Three groups of mice were fed a standard diet (STD), HFD, or HFD supplemented with pistachio (HFD-P) for 16 weeks. Metabolic parameters (oxidative stress, apoptosis, and mitochondrial dysfunction) were analyzed by using specific assays and biomarkers. The pistachio diet significantly reduced the serum levels of triglycerides and cholesterol in the HFD model. No difference was observed in the index of insulin resistance between HFD and HFD-P. A higher number of fragmented nuclei were found in HFD cerebral cortex compared to STD and HFD-P. A decrease in reactive oxygen species, singlet oxygen and phosphorylated extracellular signal-regulated kinase, and an increase of superoxide dismutase 2 and heme oxygenase expression were found in the brains of the HFD-P samples compared to HFD. Furthermore, the impaired mitochondrial function found in HFD brain was partially recovered in HFD-P mice. These results suggest that the regular intake of pistachio may be useful in preventing obesity-related neurodegeneration, being able to reduce both metabolic and cellular dysfunctions.The positive effects of the Mediterranean diet on health have been well documented [9,10]. The longevity of one Mediterranean population, over 90 years old without dementia, was attributed to the nutraceutical components of the Mediterranean diet [11]. Functional food has been reported to delay or inhibit neurodegeneration, suggesting their employment as an alternative therapeutic strategy for correlated diseases [12][13][14].Benefits of nut consumption (mainly pistachios, walnuts, and almonds) have been described in studies on both animals and humans [15,16]. Daily nut consumption can improve dysmetabolic conditions such as obesity, type 2 diabetes, and related cardiovascular diseases [17,18]. In particular, Pistacia atlantica oleoresin has been proposed as an agent that protects the body against conditions associated with oxidative stress [19], including memory impairment, in lipopolysaccharide-treated rats [20]. Nevertheless, the potential beneficial impact of nut intake on neurodegenerative disorders, as well as on other cognitive-behavioral deficits, has been poorly explored.Compared to other nuts, pistachios possess a healthier nutritional profile, with low-fat content, high content of polyunsaturated fatty acids (13.3 g/100 g) and mono-unsaturated fatty acids (24.5 g/100 g), minerals (potassium, phosphorus, magnesium, and calcium) and vitamins (vitamin A, vitamin E, vitamin C, and vitamins B). Phytochemicals of pistachio show high bioavailability, contributing to the beneficial relationship between pistachio consumption and health-related outcomes [21]. Furthermore, recent data have demonstra...

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Section: Discussionmentioning

confidence: 99%

Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice

et al. 2020

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“…ese risk factors trigger neuroinflammation and oxidativenitrosative stress. Proinflammatory cytokines, endothelin-1, and oxidative-nitrosative stress cause several cycles of pathological feedback and influence cerebrovascular pathology [63]. ese cascades lead to an increase in neuronal Ca 2+ and neurodegeneration [64].…”

Section: Obesity and Neuroinflammationmentioning

confidence: 99%

Structural Brain Changes Associated with Overweight and Obesity

et al. 2021

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Obesity is a global health problem with a broad set of comorbidities, such as malnutrition, metabolic syndrome, diabetes, systemic hypertension, heart failure, and kidney failure. This review describes recent findings of neuroimaging and two studies of cell density regarding the roles of overnutrition-induced hypothalamic inflammation in neurodegeneration. These studies provided consistent evidence of smaller cortical thickness or reduction in the gray matter volume in people with overweight and obesity; however, the investigated brain regions varied across the studies. In general, bilateral frontal and temporal areas, basal nuclei, and cerebellum are more commonly involved. Mechanisms of volume reduction are unknown, and neuroinflammation caused by obesity is likely to induce neuronal loss. Adipocytes, macrophages of the adipose tissue, and gut dysbiosis in overweight and obese individuals result in the secretion of the cytokines and chemokines that cross the blood-brain barrier and may stimulate microglia, which in turn also release proinflammatory cytokines. This leads to chronic low-grade neuroinflammation and may be an important factor for apoptotic signaling and neuronal death. Additionally, significant microangiopathy observed in rat models may be another important mechanism of induction of apoptosis. Neuroinflammation in neurodegenerative diseases (such as Alzheimer’s and Parkinson’s diseases) may be similar to that in metabolic diseases induced by malnutrition. Poor cognitive performance, mainly in executive functions, in individuals with obesity is also discussed. This review highlights the neuroinflammatory and neurodegenerative mechanisms linked to obesity and emphasizes the importance of developing effective prevention and treatment intervention strategies for overweight and obese individuals.

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“…The principal mechanisms by which adiponectin improve insulin sensitivity seems to be through augmented fatty acid oxidation and suppression of hepatic glucose production [24]. Also, NAC could ameliorate IR through down-regulation of intracellular ROS and direct free radical scavenger actions [27].…”

Section: Discussionmentioning

confidence: 99%

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

Abdelhaffez

El-Aziz

Tohamy

et al. 2020

Preprint

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Background Chronic fructose consumption is associated with development of obesity, insulin resistance (IR) and metabolic syndrome (MS). Cardiovascular diseases are linked to metabolic deregulation observed in MS. N-acetylcysteine (NAC) is a sulfur containing compound of Allium plants (such as garlic and onion) that increases intracellular reduced glutathione concentrations, which is an endogenous antioxidant. Methods This study investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced MS in male Wistar rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose (20% w/v) induced MS animals for twelve weeks. Results Chronic fructose consumption increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), IR and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP and mitigated atherogenic dyslipidaemia and oxidative stress (OS). Additionally, NAC down-regulated CT-1 expression in the heart and aorta. Furthermore, CT-1 expression in the heart and aorta was positively correlated with basal glycemia, final SBP and DBP, total cholesterol, triglycerides, low density lipoproteins and negatively correlated with high density lipoproteins levels. Conclusion The findings reported here demonstrated, for the first time, the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model. Also, our results revealed the infallible role of NAC to blunt the cardiometabolic deregulation observed in MS.

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Redox status, inflammation, necroptosis and inflammasome as indispensable contributors to high fat diet (HFD)-induced neurodegeneration; Effect of N-acetylcysteine (NAC)

Cited by 24 publications

References 43 publications

Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice

Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice

Structural Brain Changes Associated with Overweight and Obesity

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

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