New Obesity Treatment Possible With Novel Protein Discovery

According to the Centers for Disease Control and Prevention (CDC), more than one-third of US adults are now obese. But new research published in the Journal of Neuroscience details how a protein in the brain regulates food intake and body weight - opening new doors for the treatment of obesity.

The research team, led by Maribel Rios, associate professor of the department of neuroscience at Tufts University School of Medicine, say their findings may also help explain why some drugs, such as gabapentin and pregabalin, can cause people to gain weight. The investigators discovered that alpha2/delta-1 - a protein that has not previously been associated with obesity - assists the function of a protein called brain-derived neurotrophic factor (BDNF). Rios notes that in one of his previous studies, it was found that BDNF is crucial for appetite suppression. But in this most recent study, the research team found that low levels of BDNF were linked to reduced function of alpha2/delta-1 in the hypothalamus - an area of the brain that plays an important role in regulating weight and food intake. Suppressed alpha2/delta-1 protein 'causes weight gain'. Using mouse models, the investigators suppressed the alpha2/delta-1 protein. This caused the mice to consume 39% more food compared with control mice over a 7-day period, causing them to gain weight. When the protein was restored to normal and BDNF levels were reduced, the mice ate less and gained less weight. Their blood sugar levels also returned to normal. "When we re-introduced alpha2/delta-1 in obese mice lacking BDNF in the brain, we saw a 15-20% reduction in food intake and a significant reduction in weight gain," explains Rios. "Importantly, metabolic disturbances associated with obesity, including hyperglycemia and deficient glucose metabolism, were greatly reduced by restoring the function of alpha2/delta-1."

The researchers say their findings may provide new avenues for the treatment of obesity. Rios says: "We know that low levels of the BDNF protein in the brain lead to overeating and dramatic obesity in mice. Deficiencies in BDNF have also been linked to obesity in humans. Now, we have discovered that the alpha2/delta-1 protein is necessary for normal BDNF function, giving us a potential new target for novel obesity treatments." Findings may help alleviate weight-gaining side effects of medication. Some medication such as gabapentin and pragabalin - drugs used to treat epilepsy and nerve pain - can cause people to gain weight. From their research, the investigators say they believe the drugs do this by inhibiting the alpha2/delta-1 protein in the hypothalamus, and that this discovery may lead to new treatments that can halt weight gain for patients who take this medication. But for now, the team say they plan to further investigate how alpha2/delta-1 works. "We now know that alpha2/delta-1 plays a critical role in healthy BDNF function. The finding improves our understanding of the intricate neuroscience involved in appetite control," says Rios. "The next phase of our research will be to unravel the mechanisms mediating the satiety effects of alpha2/delta-1 in the hypothalamus." In a study reported in October 2013, researchers discovered that obesity may be caused by a hunger gene called KSR2. When the gene was removed from mouse models, the mice gained weight.