How fat may hurt the brain

New York Times Posted online: Saturday, Mar 08, 2014 at 0000 hrs
New York : Obesity may have harmful effects on the brain, and exercise may counteract many of those negative effects, according to sophisticated new neurological experiments with mice, even when the animals do not lose much weight. While it’s impossible to know if human brains respond in precisely the same way to fat and physical activity, the findings offer one more reason to get out and exercise.

It’s been known for some time that obesity can alter cognition in animals. Past experiments with lab rodents, for instance, have shown that obese animals display poor memory and learning skills compared to their normal-weight peers. They don’t recognise familiar objects or recall the location of the exit in mazes that they’ve negotiated multiple times.

But scientists hadn’t understood how excess weight affects the brain.

Fat cells, they knew, manufacture and release substances into the bloodstream that flow to other parts of the body, including the heart and muscles. There, these substances jump-start biochemical processes that produce severe inflammation and other conditions that can lead to poor health.

Many thought the brain, though, should be insulated from those harmful effects. It contains no fat cells and sits behind the protective blood-brain barrier that usually blocks the entry of undesirable molecules.

However, recent disquieting studies in animals indicate that obesity weakens that barrier, leaving it leaky and permeable. In obese animals, substances released by fat cells can ooze past the barrier and into the brain.

The consequences of that seepage became the subject of new neurological experiments conducted by researchers at Georgia Regents University in Augusta and published last month in The Journal of Neuroscience. For the studies, the scientists gathered mice bred to overeat and grow obese, which, after a few weeks of sitting quietly in their cages and eating at will, the animals had obligingly accomplished. As they grew rotund and accumulated more fat cells, the researchers found, their blood showed increasingly hefty doses of a substance called interleukin 1 that is created by fat cells and known to cause inflammation.

In these mice, as interleukin 1 migrated to the head, it passed the blood-brain barrier and entered areas such as the hippocampus, a part of the brain critical for learning and memory. There, it essentially gummed up the works, the researchers found when they examined tissue from the animals’ brains

But whether excessive fat cells alone were the underlying cause of the changes in the animals’ brains was not clear. Other physiological factors “could have been contributing,” said Alexis Stranahan, a professor at the Medical College of Georgia at Georgia Regents, who oversaw the study. So, to isolate the impact of the fat, the researchers simply removed most of it, surgically excising the large bands of fat that each mouse bore around its middle.

After recovery, these slenderised mice showed almost no interleukin 1 in their bloodstreams and, Algernon-like, soon were acing cognitive tests that had stumped them before surgery.

Conversely, when the scientists implanted the preserved fat pads into previously lean mice — and haven’t we all had nightmares about something like that happening to us in our sleep? — the animals almost immediately grew dimmer, performing far worse than previously on cognitive tests, although nothing else in their lives had changed.

The results convincingly implicated fat cells as the primary cause of the mice’s cognitive decline. Gathering more of the obesity-prone mice, they allowed all of them to grow heavy, but then started half on a daily 45-minute exercise session. Other mice remained sedentary.

After 12 weeks, running mice had lost fat and did much better on cognitive tests than the sedentary mice. The results suggested that, as the scientists write in the study, “treadmill training normalised hippocampal function,” even in animals born to be fat and that remained heavy.

Of course, these studies were conducted in mice, not people, whose brains may respond very differently. But the possibility that humans, too, may respond in similar ways is tantalising, Dr Stranahan said, and the takeaway from her study worth repeating. “Get out and move,” she said, even — and especially — if you carry extra weight. Talk with your doctor about a safe and tolerable exercise program, and then try to stick with that routine so that extra pounds won’t weigh too heavily on your mind.

- GRETCHEN REYNOLDS