Australian researchers have discovered a novel method to treat obesity by directly blocking a receptor within fat cells and speeding up energy expenditure. A promising experimental drug has been developed targeting this receptor and it has been effective at preventing obesity in mice.
Neuropeptide Y (NPY) is a peptide produced by the central nervous system and is known to play a role in various physiological processes. High levels of NPY are linked to increased appetite and weight gain, while low levels increase energy expenditure, helping the body burn fat instead of storing it.
“NPY is a metabolism regulator that plays a critical role during states of low energy supply, where it helps store fat as a survival mechanism,” explains Herbert Herzog, co-senior author on the new study. “Today, however, these advantageous effects can exacerbate existing diet-induced weight gain, leading to obesity and metabolic disease.”
One of the key cellular receptors NPY uses to exert its effects is called Y1. The new study set out to explore whether blocking Y1 receptor activity in peripheral tissues could increase fat metabolism and essentially prevent weight gain.
Using a mouse model of obesity the researchers tested an experimental drug designed to block Y1 signaling in fat tissue called BIBO3304. Yan-Churn Shi, co-senior author on the new study, says after about seven weeks on a high-fat diet the BIBO3304 mice had gained 40 percent less weight than a control group on the same diet.
“This significant reduction of body weight gain was caused by an increase in body heat generation and reduction in fat mass,” says Shi. “Further, when [we] applied BIBO3304 to human fat cells isolated from obese individuals, we found that the cells began switching on the same genes involved in producing heat as the ones in mice, which suggests that targeting the Y1 receptor pathway may similarly increase fat metabolism and reduce weight gain in humans.”
The most promising aspect of the new research is how Y1 receptor signaling seems to be primarily limited to fat cells. Prior attempts to inhibit NPY mechanisms have led to broad systemic side effects, making it unfeasible as an anti-obesity treatment, but homing in solely on Y1 receptors may be the key to getting this treatment to work.
Not only did the researchers discover BIBO3304 does not cross the blood-brain barrier, meaning it will not disrupt other NPY processes in the brain, but there may be secondary benefits to blocking Y1 signaling, including improvements to insulin resistance and cardiovascular function.
Of course, it’s still early days for the research, with plenty more work to be done before an anti-obesity drug for humans can be tested. But the big promising discovery here is that there is great potential for preventing obesity by disrupting this NPY-Y1 receptor system.
“Most of the current medications used to treat obesity target the brain to suppress appetite and can have severe side effects that limit their use,” says Shi. “Our study reveals an alternative approach that targets the fat tissues directly, which may potentially be a safer way to prevent and treat obesity.”
The new study was published in the journal Nature Communications.
