System biology approach intersecting diet and cell metabolism with pathogenesis of brain disorders

Abstract

The surge in meals high in calories has prompted an epidemic of metabolic disorders around the world such that the elevated incidence of obese and diabetic individuals is alarming. New research indicates that metabolic disorders pose a risk for neurological and psychiatric conditions including stroke, Alzheimer’s disease, Huntington’s disease, and depression, all of which have a metabolic component. These relationships are rooted to a dysfunctional interaction between molecular processes that regulate energy metabolism and synaptic plasticity. The strong adaptive force of dietary factors on shaping the brain during evolution can be manipulated to trans form the interaction between cell bioenergetics and epigenome with the aptitude to promote long-lasting brain healthiness. A thorough understanding of the association between the broad action of nutrients and brain fitness requires high level data processing empowered with the capacity to integrate information from a multitude of molecular entities and pathways. Nutritional systems biology is emerging as a viable approach to elucidate the multiple molecular layers involved in information processing in cells, tissues, and organ systems in response to diet. Information about the wide range of cellular and molecular interactions elicited by foods on the brain and cognitive plasticity is crucial for the design of public health initiatives for curtailing the epidemic of metabolic and brain disorders.

Diet and depression: exploring the biological mechanisms of action

“…In vitro cell culture experiments and rodent studies have shown that restriction or surfeit of macronutrients have reproducible effects on multiple epigenetic mechanisms on many different genes including those involved in metabolism and behaviour [167,168]. Metabolic perturbations are becoming known as a driving force for genomic and epigenomic alterations by which the effects of diet are saved in the genes [169]. Components of nutrient-rich dietary patterns including vitamins such as folate, biotin, B6 and B12; polyphenols such as curcumin, resveratrol and genistein [170]; and omega-3 fatty acids [171] have all been shown to influence epigenetic state through multiple mechanisms.…”

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer’s Disease

“…The disturbances in cell energy metabolism pose a heavy toll for the maintenance of neuronal connectivity and function which can accelerate the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (Gomez-Pinilla and Yang, 2018 ). Synaptic communication is essential for neuronal function and cognition and highly demanding on energy such that disruptions in cell metabolism associated with fructose can heavily damage overall brain function, beyond simply cell survival.…”

“…While the amyloid cascade hypothesis has not been discounted, other hypotheses are now receiving attention, including the role of cerebral insulin resistance and glucose hypometabolism (Neth and Craft, 2017 ), neuroinflammation (characterized by high cytokine levels at sites of tissue degeneration), synaptic dysfunction, and the role of mitochondrial dysfunction with alterations in intracerebral ATP levels (Demetrius et al, 2014 ; de la Monte, 2017 ; Cenini and Voos, 2019 ). There is also evidence that Alzheimer’s disease may be linked with obesity and diabetes, and with the western diet (Arvanitakis et al, 2004 ; Gomez-Pinilla and Yang, 2018 ). However, while obesity and diabetes are risk factors for Alzheimer’s disease (Arnold et al, 2018 ), Alzheimer’s disease may occur in the absence of these conditions.…”

Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer's disease: 30 years of clinical use

“…46,131,132 Finally, physical activity, dietary restriction, some foods, and social interaction could contribute to foster neuronal resilience and delay AD onset and progression by increasing brain BDNF expression. [133][134][135][136][137][138][139][140]…”

“…Several drugs used for controlling AD risk factors such as diabetes, hypertension, hypercholesterolemia, depression, and stress may also enhance BDNF 46,131,132 . Finally, physical activity, dietary restriction, some foods, and social interaction could contribute to foster neuronal resilience and delay AD onset and progression by increasing brain BDNF expression 133–140 …”