In a recent study published in the journal Journal of Endocrinology a team of researchers from the University of Florida and Oregon State University found that delivering the hormone leptin directly to the brain through gene therapy aids weight loss without the significant side effect of bone loss.
Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can have detrimental side effects, including accelerating age-related bone loss.
Moreover, the long-term efficacy of conventional weight loss interventions is generally poor and many individuals cycle through repetitive bouts of weight loss followed by rapid weight regain.
“Weight loss is generally good for you if you are seriously overweight, but bone loss can cause significant problems later in life,” said Urszula Iwaniec, an associate professor in the College of Public Health and Human Sciences at OSU in a news release. “What we are trying to determine is whether there is a way to lose excessive weight while preserving bone density.”
The adipokine leptin plays an essential role in energy homeostasis, and adult-onset weight gain is closely associated with an increase in circulating leptin and development of leptin resistance. However, according to Iwaniec, people appear to develop leptin resistance with weight gain, and the brain no longer receives accurate messages.
In the study entitled “Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss,” the researchers examined that rats that received leptin had a reduction in weight of about 20%, without any bone loss. The rats that lost weight maintained that weight loss. These rats were also found to have large reductions of abdominal fat, known to contribute to weight-related health problems.
“Using leptin at the level of the hypothalamus to control weight is where, at some point, we believe we’re going to be able to control weight gain,” she said. “When the brain tells us to lose weight, it works. When we try to lose weight and the brain tells us not to, it doesn’t work.”
To better understand the role of leptin in weight and bone loss, the team of investigators injected the leptin gene into the rat’s hypothalamus and explored the effects on the rat’s weight and bones. According to Iwniec, the injection of leptin into the brain lets the hormone bypass the blood-brain barrier, which reduces the ability of leptin to enter the brain.
This type of gene therapy is permanent, which may lead to other side effects or risks that remain unknown, so more research is necessary before such therapy becomes a treatment for human weight loss.
“This kind of therapy has the potential for being far less invasive than something like bariatric surgery,” Turner said. “But it’s forever. It seems like a very extreme procedure, from that standpoint.”
