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“…an interconnected phenomenon between metabolic disorders and disorders of the brain.”

The parallel rise of modern chronic non-infectious diseases such as obesity and neurodegenerative diseases is difficult to ignore. In the past few years, the relationship between these seemingly distinct conditions has emerged as an interconnected phenomenon between metabolic disorders and disorders of the brain.

Obesity, characterized by an excessive accumulation of body fat, has evolved into a global epidemic. Simultaneously, neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are on the rise, posing significant challenges to healthcare systems worldwide. It is projected that by 2030 nearly half of all US adults will be obese. It is also estimated that cases of dementia in the “developed world” will rise from 21.2 million in 2025 to 36.7 million in 2050.

Recent studies have shed light on the potential connection between these conditions, suggesting that obesity may serve as a catalyst for the development and progression of neurodegenerative disorders.

“Adipose tissue, specifically in obese individuals, acts as an active endocrine organ, secreting pro-inflammatory molecules.”

One of the primary links between obesity and neurodegenerative disease lies in chronic low grade engagement of the immune system. Adipose tissue, specifically in obese individuals, acts as an active endocrine organ, secreting pro-inflammatory molecules. These molecules trigger a state of chronic low-grade inflammation, which not only contributes to metabolic disturbances but also has detrimental effects on the brain. The persistent inflammation can potentially accelerate the progression of neurodegenerative processes. Interestingly, in lean individuals, however, adipose tissue “predominantly secretes anti-inflammatory markers”.

“…metabolic dysregulation not only heightens the risk of type 2 diabetes but also impairs brain function.”

Moreover, insulin resistance, a hallmark of obesity, has emerged as another factor in the obesity-neurodegeneration connection. In insulin-resistant individuals, cells become less responsive to insulin, leading to insulin spikes as well as increased blood sugar levels. This metabolic dysregulation not only heightens the risk of type 2 diabetes but also impairs brain function.

Research suggests that insulin resistance impairs neuronal function, and a recent study found that an obesogenic diet effectively “delays the clearance of neuronal debris”. Clearance of neuronal debris by microglia is imperative to prevent “inflammation, neuronal death, and poor nervous system recovery.” Without clearance of neuronal debris, degeneration prevails over regeneration.

“…there is a direct link between a high sugar diet and defects in microglial functioning.”

The study further explains that glial function affects “feeding behavior, weight, and systemic metabolism, suggesting that diet may play a role in regulating glial function.” Since a high sugar diet, when administered to fruit flies, triggers insulin resistance in glia, there is a direct link between a high sugar diet and defects in microglial functioning.

“…obese individuals tend to express more learning and memory deficits than do leaner individuals.”

Additionally, research on the brain gut microbiome system, as discussed many times in this blog, sheds light on the emerging obesity-neurodegeneration connection. The gut microbiota, influenced by obesity-related factors like diet as well as stress, profoundly impacts brain health. Alterations in the gut microbiome in obese individuals may lead to the production of metabolites that affect neuronal function and contribute to neurodegenerative processes. As a result, obese individuals tend to express more learning and memory deficits than do leaner individuals.

Furthermore, lifestyle factors associated with obesity, such as poor diet and physical inactivity, play a major role in the onset and progression of neurodegenerative disorders. Diets high in ultra-processed foods, refined sugars and refined carbohydrates not only contribute to weight gain but also adversely impact brain health. Conversely, physical activity has been shown to exert neuroprotective effects, potentially mitigating the risk of neurodegeneration.

“Not all obese individuals develop neurodegenerative diseases…”

While the association between obesity and neurodegeneration is becoming increasingly evident, it is important to acknowledge that many other factors contribute to the onset of disease. Not all obese individuals develop neurodegenerative diseases, and of course not all individuals suffering from neurodegenerative diseases are obese. This indicates the presence of other mechanisms and potentially even protective factors.

Nonetheless, understanding the connection between obesity and neurodegeneration is important in order to reverse the growing tide of early cognitive decline. Targeted interventions and education such as promoting healthy diet and lifestyle habits as well as optimizing metabolic health may help to mitigate the rise of neurodegenerative diseases.

“…it is important to stay active, eat a nutrient dense diet, manage stress and prioritize high quality sleep.”

Based on ongoing research, there is likely a strong link between metabolic and cognitive diseases, with low grade activation of the immune system playing a key role. Diet, lifestyle and environmental factors all play a role in the onset of both obesity and neurodegenerative disorders. In order to support your own metabolic health and brain health, it is important to stay physically and mentally active, eat a Mediterranean style diet, manage stress and prioritize high quality sleep.