How Eating a High-Fat Diet Affects My Brain

Hello, my name is Anthony Oppong-Gyebi, a third year PhD student at the University of North Texas Health Science Center.

The food we eat affects the body in diverse ways, both positively as a requirement for normal bodily function, and negatively as a factor for increasing risk of certain diseases. Fat foods as part of the essential nutrients have come under a lot of scrutiny because of a stronger link with numerous diseases.

In this video, I outlined how routine intake of a high-fat diet over long periods leads to changes in the gut microbiota where a possible increase in the risk of stroke. Large intake of fat meals for a long time can cause an imbalance in the gut flora by altering the microbial diversity, most especially favoring the population of gram-negative bacteria.

Increased population of gram-negative bacteria further increases the levels of lipopolysaccharides which form part of the outer cell membrane. The presence of the lipopolysaccharides can cause dysfunction of the intestinal tight junctions, thereby increasing the permeability of the intestines to more lipopolysaccharides and other toxins. These toxins enter the bloodstream where they act as pathogen associated membrane patterns to activate immune cells, including macrophages leading to a chronic inflammatory state.

This is characterized by increased nuclear factor kappa B (NfkB) signaling, sustained cytokine production and macrophage accumulation. Under chronic inflammatory conditions, oxidative stress ensues which promote the formation of oxidized low-density lipoproteins. As oxidized low-density lipoproteins wander in the bloodstream, they adhere to one another and to the walls of the vasculature leading to the formation of atheromatous plaques both in the periphery and centrally.

Blockade of a major artery like a middle cerebral artery by an atheroma formation reduces cerebral blood flow and subsequently cerebral ischemia. Under low oxygen and glucose concentration as a result of hypoperfusion to the neurons, the Na+/K+/ATPase, a transmembrane pump for maintenance of resting membrane potential of the neurons fails, thereby causing membrane depolarization.

This is followed by activation of voltage-gated NMDA and AMPA receptors to cause an avalanche of calcium ions into the cell resulting in excitotoxicity. The large intracellular calcium ions are taken up by the mitochondria, triggering the release of large amounts of cytochrome C, a component of the electron transport chain and intrinsic apoptotic pathway.

Cytochrome C together with apoptotic protease activating factor one (Apaf-1) form apoptosome. Apoptosome is a protein complex which initiate activation of downstream caspases to cause neuronal death. With a high susceptibility of neurons to ischemic injury, the neurons within this ischemic area die quickly and are replaced by glial cells, a phenomenon described as glial scarring. This prevents restoration of the lost neurons and hence causes permanent motor and cognitive impairments over time.

Ischemic stroke can further cause the release of large amounts of damage associated molecular toxins and cytokines into the periphery. This can cause protracted dysbiosis of the gut microbiota and increased permeability of the gut to bacteria and toxins, a process which can result in septicemia and ultimately death after stroke.

Knowing the detriments of a high-fat diet, it’s advisable to eat healthy to protect the brain from cerebral vascular diseases including ischemic stroke.

Thank you for watching this video.