Healthy eating and exercise are doctors’ top two recommendations to treat a wide range of ailments. Unfortunately, New Years’ resolutions for fitness often find their way to an early February grave, and we dismiss these lifestyle changes that could save our lives. The barriers to exercise involve both time and access, and the convenience of unhealthy food often outweighs a balanced diet. The latter was dramatically portrayed in the documentary Super Size Me, which followed one man’s monthlong descent into sedentary binge-eating. While diet and exercise are suggestions at the macro level, there is a molecular basis to physician-recommended changes. Scientists have found a molecule that links functions in the brain to obesity, diabetes, and cancer. This molecule, brain-derived neurotrophic factor (BDNF), is a signal from the part of the brain that regulates body mass. As a result, varying BDNF levels dramatically impacts overall health.
Studying lifestyle changes in mice
Researchers already know that obesity is one of the leading causes of breast cancer, and the Ohio State University research group led by Dr. Lei Cao realized that BDNF could be the culprit when they noticed that improving living conditions lowered obesity and cancer risk in mice.
Researcher Grant Foglesong described the improved conditions to include “increased living space that could house more mice, leading to a more advanced social hierarchy.” In addition to stimulation from social interactions, “The mice also had toys to play with, like tunnels and running wheels, which normal lab mice don’t get.”
The mice living in this improved environment had higher levels of BDNF in the hypothalamus, which is the part of the brain that controls body mass. This led researchers to ask whether increasing BDNF in mice living in standard lab conditions would lower their susceptibility to obesity and cancer without changing their lifestyles.
A new fate for Supersized mice
Similarly to filmmaker Morgan Spurlock eating three McDonalds meals per day and not exercising, the lab mice were fed a fatty diet without access to exercise wheels. After one year, the mice had become morbidly obese and diabetic. When researchers injected extra BDNF into the hypothalamus, the mice became noticeably healthier, even though their diet and activity level were unchanged.
With increased BDNF, the obese mice returned to a healthy body weight. Although they continued to eat the fatty diet, after ten weeks they were able to reach and maintain a healthy body weight. Alongside the reduction in fat tissue, researchers saw improved health in the mice in terms of other obesity-related diseases.
Type II diabetes, where patients still produce insulin, but their bodies can no longer use it, is one disease related to obesity. Because obese mice lack proper insulin response, they typically have an exaggerated spike in blood sugar after a glucose injection. The mice treated with BDNF were better able to manage a sudden glucose spike, showing that their bodies could now respond to insulin.
After reversing obesity-induced diabetes using BDNF, the Cao group turned to the link between obesity and cancer. Prognosis in cancer patients is typically worsened in obese individuals. However, the obese mice treated with BDNF were able to slow tumor growth after an injection of breast cancer cells. These promising results will drive research for a possible therapy to treat both obesity and breast cancer.
So can we have our cake and eat it too?
Following a regular exercise regimen and maintaining a balanced diet increases BDNF levels in humans. So, can we skip the healthy lifestyle and just inject ourselves with BDNF?
“Well no,” Foglesong cautioned. “Increasing BDNF levels in human patients would involve brain operations that could prove risky.”
Still, there is hope that being able to target the brain-cancer connection will mitigate the difficulties in following medical advice. “If we can develop a less invasive BDNF treatment, we will be able to reverse obesity and potentially prevent cancer.”
***This was based on an article published in Molecular Therapy and an interview with (soon-to-be Dr.) Grant Foglesong.
Mol Ther. 2014 Jul;22(7):1275-84. doi: 10.1038/mt.2014.45. Epub 2014 Mar 18.
Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice.