Reducing fat through exercise in obese, diabetic mice improved their memory and brain function, new research from Georgia Regents University found.
The same good effect could be gained by surgically removing the fat but so far it has only been shown in mice genetically bred to be obese and it might not last, said GRU neuroscientist Alexis M. Stranahan.
The research comes as a new report published today in the Journal of the American Medical Association found that obesity levels are virtually unchanged from eight years ago and remain high across all age groups from babies to senior citizens, except for a surprising decline among children ages 2 to 5.
Previous work by Stranahan and others had shown that the mice specially bred to become obese and diabetic also do worse on memory tests than normal mice. But in her study with GRU colleagues in the Journal of Neuroscience, regular exercise on a treadmill at less than half what normal mice might do turned that around.
“The interesting aspect of these findings was that the exercise abolished the impairment entirely” in memory tests, such as navigating a maze, Stranahan said.
The researchers also looked to see if that showed up in better brain function, particularly in the hippocampus, “which is a brain region that is critical for learning and memory, and it is also selectively vulnerable during aging and Alzheimer’s disease,” she said.
The sedentary mice had dysfunction, but in the exercising mice “the treadmill brought it back,” Stranahan said. “And it is reversible in a fairly extreme genetic model of obesity.”
The fat is inducing inflammation in the brain that is leading to the impairment, and Stranahan was able to focus in on a particular messenger called interleuken-1 beta. There is already a drug that counteracts that inflammatory signal approved by the Food and Drug Administration to treat rheumatoid arthritis called anakinra or Kineret.
In order to show that it was the fat and not the exercise that was driving the results, the researchers removed the visceral fat akin to human belly fat and got the same good results, while transplanting that fat into normal mice induced the same mental impairments as the obese diabetic mice.
Stranahan knows that many people will read the surgical result and believe the improvement was from “mouse liposuction,” she said. But it is not that easy.
The GRU work was done fairly soon after surgery and in other similar mice who had the visceral fat removed, “their other fat depots compensated by expanding and spreading and re-establishing their high level of (fatness),” Stranahan said.
“In terms of a long-term effect I don’t think really drastic liposuction is going to be an effective therapeutic strategy.”
Stranahan’s work is now moving away from using mice genetically bred to get obese and moving toward mice who get obese through diet, which is closer to the human model. But her work reinforces a tried-and-true message for people.
“Exercise is the best medicine,” Stranahan said, particularly in light of the study in JAMA that found, compared to data from 2003-04, the rates of obesity in 2011-12 for children ages 2-19 remained around 17 percent and more than a third of adults – 34.9 percent – were obese. The rate for 2- to 5-year-olds declined from 14 percent to 8 percent.
“In terms of childhood obesity we certainly shouldn’t be canceling PE (physical education),” Stranahan said. “And we need to incentivize physical activity in people somehow. There needs to be some kind of push because it is not going to happen by a magic bullet.”