A receptor that helps conserve energy when food is scarce may be the key to a safer approach to treating diet-induced obesity, research conducted by the Garvan Institute of Medical Research has found.
In a study using experimental models and fat tissue biopsies from obese individuals, the team found that blocking a specific receptor for the neuropeptide Y molecule (NPY), which helps our body regulate its heat production. , could increase fat metabolism and prevent weight gain.
“The Y1 receptor acts as a ‘brake’ on the production of heat in the body. In our study, we found that blocking this receptor in fatty tissue turned “energy storing” fat into “energy burning” fat, which ignites heat. production and reduced weight gain, ”says Dr. Yan-Chuan Shi, head of the neuroendocrinology group at Garvan and co-lead author of the article published in Nature communications.
“Most of the drugs currently used to treat obesity target the brain to suppress appetite and can have serious side effects that limit their use. Our study reveals an alternative approach that directly targets fatty tissue, which can potentially be a safer way to prevent and treat obesity. “
Y1 receptor linked to obesity
Obesity and overweight are major public health problems that are estimated to affect two-thirds of all adults. The disease can lead to serious medical complications, including diabetes, cardiovascular disease, and some cancers, and although lifestyle changes are essential for weight loss, medications are a crucial adjunct treatment option for some. .
The study authors studied Y1 receptors controlled by the NPY molecule, which is released in the body under starvation conditions to help reduce energy expenditure and increase fat storage. Surprisingly, the team found that Y1 receptors were produced at higher levels in the fat tissue of obese people.
The team then blocked the Y1 receptor using the experimental treatment BIBO3304 in a mouse model of obesity.
“In our study, we found that mice given BIBO3304 and fed a high fat diet gained about 40% less body weight in seven weeks than mice given a high fat diet alone. This significant reduction in body weight gain was caused by an increase in body heat production and a reduction in body fat, ”says Dr. Shi.
“In addition, when we applied BIBO3304 to human fat cells isolated from obese individuals, we found that the cells began to activate the same genes involved in heat production as those in mice, suggesting that targeting of the Y1 receptor pathway can similarly increase fat metabolism and reduce weight gain in humans, ”adds Dr. Shi.
Targeting obesity at the source
“NPY is a metabolic regulator that plays an essential role in states of low energy intake, where it helps store fat as a survival mechanism.” Today, however, these beneficial effects may exacerbate diet-induced weight gain, leading to obesity and metabolic disease, ”says co-lead author Professor Herbert Herzog, head of the Disorders Laboratory. food at Garvan.
The researchers say that a crucial part of the study was to demonstrate that the experimental treatment BIBO3304 did not cross the blood-brain barrier and that the anti-obesity effects of blocking the Y1 receptor pathways did not occur via the brain, but only in peripheral tissues. .
“Most of the treatments currently prescribed aim to reduce food intake by targeting the central nervous system. However, they can have significant psychiatric or cardiovascular side effects, which have led to more than 80% of these drugs being withdrawn from the market, ”explains Dr Shi. .
“Our study is crucial evidence that blocking Y1 receptors in peripheral tissue without affecting the central nervous system is effective in preventing obesity by increasing energy expenditure. It reveals a new therapeutic approach that is potentially safer than current drugs that target appetite, ”says Professor Herzog.
“Our team and other groups have revealed other potential benefits by targeting the NPY-Y1 receptor system, including stimulating bone cell growth and improving cardiovascular function and insulin resistance. “, he adds. “We hope that the publication of our results will generate increased interest in the exploration of BIBO3304 and related agents as potential treatments for obesity and other health problems.”
This research was funded by the National Health & Medical Research Council of Australia and a grant from the Diabetes Research Program in Australia.