Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases

Flores-Dorantes, María Teresa; Díaz-López, Yael Efren; Gutiérrez-Aguilar, Ruth

doi:10.3389/fnins.2020.00863

Cited by 82 publications

(70 citation statements)

References 370 publications

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“…Obesity is an important risk factor for the onset and progression of various neurodegenerative diseases. Parkinson's disease, Alzheimer's disease, and multiple sclerosis can be initiated by various metabolic changes related to the damage of the CNS caused by obesity [128]. ese changes can alter synaptic plasticity of neurons and lead to neuronal death, affecting normal physiology of the CNS [49,129].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Structural Brain Changes Associated with Overweight and Obesity

et al. 2021

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“…Hyperglycemia in T2DM increases AD risk by exacerbating microglia and astrocyte-mediated neuroinflammation and neuronal injury [ 297 ]. Individuals with advanced age, obesity, T2DM, or hypercholesterolemia are more likely to be affected by AD [ 298 , 299 ].…”

Section: Meta-inflammation (Metaflammation)mentioning

confidence: 99%

Neuroinflammation in Alzheimer’s Disease

et al. 2021

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Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

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“…Additionally, these effects in animals have been found to be reversed by 7,8-dihydroxyflavone, a brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) agonist, which mechanistically may reverse glucocorticoid receptor phosphorylation (44). This finding in particular is important to this investigation, as BDNF hypermethylation has been previously reported as a link between obesity and depression in addition to its role in schizophrenia pathophysiology (10,12,45). Taken together then, these data suggest that the both the metabolic and behavioral effects of MSG may occur through epigenomic modulation potentially impairing the hypothalamic-pituitary-axis (HPA) feedback inhibition.…”

Section: Discussionmentioning

confidence: 87%

“…In addition to glutamate neurotransmission, epigenomic relationships between obesity, cardiovascular disease, psychosis, and depressive symptoms have been reported (10). In particular, hypermethylation of genes common to known obesity and depression pathways [i.e., Brain Derived Neurotropic Factor (BDNF)] may trigger various inflammatory cascades, which link diet, obesity, and depressive symptoms (10)(11)(12). This work also supports findings reported by our group examining gene specific methylation differences between schizophrenia and cardiovascular risk factors (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia

et al. 2021

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Introduction: Schizophrenia is a lifelong condition associated with several comorbid conditions such as physical illnesses like obesity, as well as co-occurring psychiatric symptoms such as depression. Research regarding susceptibility to some of these comorbidities has primary focused on genetic risks or neurotransmitters and very little work has been done to understand environmental factors such as diet. In particular, understanding the role of dietary glutamic acid consumption on co-morbidities in patients with schizophrenia is important, as evidence suggests that glutamic acid consumption may directly influence glutamatergic neurotransmission; a key neurotransmitter related to schizophrenia, its associated co-morbidities, and depression. Therefore, the aim of this study was to examine the potential relationship between dietary glutamic acid and depressive symptomatology in patients with schizophrenia, stratified by obesity status, due to its relationship with inflammation, antipsychotic use, and depressive symptoms.Methods: Subjects included in this analysis, were part of a parent cross-sectional study in which included three dietary recalls analyzed using protocols outlined as part of the National Health and Nutrition Examination Surveys (NHANES) standardized criteria. Additionally, body mass index (BMI), and Beck Depression Inventory were obtained at this visit. Subjects with a BMI ≥ 30 kg/m2 were included in the obesity group, and the relationship between glutamic acid consumption and BDI scores was analyzed after controlling for age, race, sex, antidepressant and antipsychotic use, and animal and vegetable protein intake which provide natural forms of dietary glutamic acid.Results: A total of 168 participants were included in this study, of which 42.5% were female and 52.9% were White. The mean BMI for the group as a whole was 33.5 ± 8.7 (kg/m2) and the mean BDI was 14.5 ± 10.2 (range 2–50). No differences were found between obesity groups, other than a greater hyperlipidemia, hypertension, and lower waist to hip ratio. Overall, no relationship was found between dietary glutamic acid and BDI scores, However, for non-obese participants, diets higher levels of glutamic acid were associated with greater depression symptomatology (p = 0.021).Conclusion: These preliminary results indicate a possible correlation between dietary glutamic acid a depressive symptoms in non-obese patients with schizophrenia, although further research is needed to specifically examine this relationship.

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Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases

Cited by 82 publications

References 370 publications

Structural Brain Changes Associated with Overweight and Obesity

Structural Brain Changes Associated with Overweight and Obesity

Neuroinflammation in Alzheimer’s Disease

Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia

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