Cognitive decline in obese diabetic mice can be reversed with regular exercise, surgical removal of belly fat


Cognitive decline that often accompanies obesity and diabetes can be reversed with regular exercise or surgical removal of belly fat, scientists report.


A drug already used to treat rheumatoid arthritis also helps obese/diabetic adult mice regain their ability to learn and comprehend, while transplanting belly fat to a normal mouse reduces those abilities, said Dr. Alexis M. Stranahan, neuroscientist at the Medical College of Georgia at Georgia Regents University.


Studies in humans and animals indicate that obesity and diabetes – which often go hand in hand – essentially triple the risk of mild cognitive impairment as well as Alzheimer’s. Stranahan focused on the effect of fat- and diabetes-associated inflammation in the brain‘s hippocampus, the center of learning and memory.


“These obese diabetic mice have very high levels of inflammatory cytokines and I think it’s because their bodies are reacting to the invasion of fat into tissues where it does not belong,” said Stranahan, corresponding author of the study in The Journal of Neuroscience. “It’s almost as if the fat were an external pathogen.”


Cytokines are major components of an immune response that typically targets invaders such as viruses. “They kind of mobilize all the natural killer cells and macrophages to kill off whatever is causing the pathogenic environment,” Stranahan said. After clearing debris or danger, cytokine levels should subside. However in obesity, fat appears viewed as a chronic invader that keeps levels of interleukin-1 beta and inflammation high.


Like a perfect storm, obesity also weakens the protective blood-brain barrier, easing access of high interleukin-1 beta levels to the brain.


Inside the brain, interleukin-1 beta turns normally supportive microglial cells predatory. Microglia typically scarf up trash and infectious agents in the brain but when interleukin-1 beta binds to their receptors, microglia signal neurons to malfunction. Microglia then consume neuronal synapses, the major points of communication between brain cells. “This interleukin-1 beta signal makes them predatory. They eat them up,” Stranahan said.


Exercise and surgery lower levels of the troublemaker in the body, so it doesn’t affect the brain while the cytokine antagonist sequesters interleukin-1 beta so it can’t reach receptors on the neurons or microglia.

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