Obesity increases risk of age-related cognitive decline and is accompanied by peripheral inflammation. Studies in rodent models of obesity have demonstrated that impaired hippocampal function correlates with microglial activation, however, the possibility that neuron/microglia interactions might be perturbed in obesity has never been directly examined. Now, a study from researchers at Augusta University has shown that when a high-fat diet causes a person to become obese, it also appears to prompt normally bustling immune cells in the brain to become sedentary and start consuming the connections between neurons. The team state that their findings show that microglia eating synapses, which is contributing to cognitive impairment in obesity, is a completely reversible condition.
Previous studies show that obesity is associated with an increased risk of development of mild cognitive impairment, late-life dementia and Alzheimer’s disease. The relative risk of the development of dementia and Alzheimer’s disease for obese and overweight individuals in midlife compared to normal weight individuals was was heightened. Epidemiological studies have shown that obesity in middle age increases the risk of developing dementia and Alzheimer’s disease, irrespective of associated medical conditions such as diabetes or vascular disease. Animal models, which allow for more accurate control of diet than studies in humans, have also found that there is a detrimental effect of diet-induced obesity on cognition. In high-fat feeding models of obesity, impairments of working memory, learning and memory performance have been observed. A recent rodent study showed that consumption of a high fat diet for 3 months caused obesity, insulin resistance, and poor performance in short-term information retention and executive function-based tests. However, the actual biological and medical-based mechanisms involved in this growing trend remain unclear.
The current study investigated normal male mice, one group ate a diet in which about 10% of the calories came from saturated fat, and another consumed chow that was 60% fat. At four, eight and 12 weeks, the lab took a series of metabolic measures, such as weight, food intake, insulin and serum glucose levels. In the hippocampus they also measured levels of proteins which correlate with the number of synapses, as well as inflammatory cytokines. Results show that all levels in both groups were essentially the same at four weeks; the mice on a high-fat diet were fatter, however other measures were normal at eight weeks. Data findings show that by 12 weeks the fat-eating mice were obese, had elevated cytokine levels and a reduction in the markers for synapse number and function.
The group then switched half the mice on the high-fat diet to the low-fat regimen. Results show that it took approximately two months for their weight to return to normal, although their overall fat pad remained larger than their peers who had never gained weight. The team explain that this fat layer makes it easier to gain weight in the future. They go on to add that the mice that remained on the low-fat diet slowly accumulated a little weight as they aged. In contrast, findings show that the group that stayed on the high-fat diet kept getting fatter, more inflamed and losing synapses. The researchers state that their microglia’s little processes, or protrusions, which normally help monitor synaptic function and help these cells move, continued to wither; dendritic spines on neurons, which get input from synapses, similarly withered on the high-fat diet, and like the microglial processes were restored with the lower-fat diet.
The team surmise that obesity yields extreme overkill in microglia, which are typically extremely discriminating and helpful to neurons. For the future, the researchers state that the findings also point to some potential new purposes for existing drugs now used for conditions such as rheumatoid arthritis and Crohn’s disease, which block specific inflammatory cytokines and tumor necrosis factor alpha, both of which are elevated in the brains of the fat mice.
Michelle is a health industry veteran who taught and worked in the field before training as a science journalist.
Featured by numerous prestigious brands and publishers, she specializes in clinical trial innovation--expertise she gained while working in multiple positions within the private sector, the NHS, and Oxford University.