New research suggests long term high dietary fat intake may influence immune cells to become sedentary and start metabolising synapses within the brain. This may have relevance to a number of neurological conditions.
How and why the immune system is affected by a long term high fat diet was the aim of a study by Hao and colleagues which appears in the journal Brain, behaviour and immunity. It was undertaken based on previous knowledge of how a high fat diet may be correlated with cognitive deterioration, concomitant peripheral inflammation and by findings which suggested microglial activation lead to hippocampal dysfunction. The team aimed to discover using mice whether a change from a high fat to a reduced fat diet may reverse the immune and neuronal responses. Two groups of mice were created to verify this, one on a high fat diet, one group on a reduced fat diet and another which started on a high fat diet and switched to a reduced fat diet for 2 months after an initial 3-month period. The mice were given identical amounts of calories with the important difference being the fat content of the food given.
The findings demonstrated how high fat levels impair hippocampus dependent memory and leads to diminished synaptic connections, the diet encouraged the activation of hippocampal microglia detected by increased evidence of biological markers. A high fat diet may encourage a hippocampal immune response involving inflammation and synaptic connections to be consumed by microglia at a higher rate three months after the high fat diet began. Mice given a diet change from a high fat diet to a reduced fat diet showed decreased synaptic pruning and microglial markers were reduced to a similar level as mice on a reduced fat diet, although weight gain may have been only partially affected by the change in diet.
Stranahan co-author commented “The fat layer makes it easier to gain weight in the future and the mice which remained on the reduced fat diet, slowly accumulated a little weight as ageing progressed.” Too much fat in the body produces chronic inflammation and this activates microglia to engage in an autoimmune response. These microglia usually move around the brain when in a resting state however during a high fat diet this ceases, microglia cease moving and start ingesting the synapses and the end result is inefficient learning. The reason for this may be because high fat content affects the microglia’s protrusions which support movement along with alteration’s to the dendritic spines of neurons. However, these protrusions and dendritic spines were restored with an adoption of a reduced fat diet.
Microglia, essential glial cells exist to support neurons within the central and peripheral nervous system which constitute 10-15% of all brain cells and, have important and distinct functions in relation to immune responses, digesting waste, foreign contaminants and objects the cells recognise as different from the proteins of healthy cells. A survey of its regional environment is enacted where foreign substances, impaired or apoptotic cells, tangles or plaques are identified and then may activate to phagocytose (digest) the material, an important immune function. The particles absorbed by the microglia are then digested freeing the body or brain from infection. When Elie Metchnikoff first discovered macrophages in 1908 winning the Nobel Prize, Elie stated the key to immunity was to “stimulate the phagocytes”.
The study by Hao and colleagues may have additional support by studies linking cholesterol metabolism to Alzheimer’s pathogenesis and genes which regulate lipids may additionally play a role in the condition. However, other studies linking the alleviation of epilepsy to a ketogenic diet may provide evidence for the importance of fat to brain functioning and fat in the diet may be beneficial for the normal functioning and development of the brain. Stranahan co-author commented, “The entire metabolic phenotype is driven by diet composition rather than the amount of calories.” High fat levels stimulate over ingestion of healthy cells by microglia which usually support the neurons and prune synapses.
How might health officials use the new study’s findings, to better implement changes in national diet recommendations?