A new study is looking to treat obesity by turning ‘energy-storing’ fat into ‘energy-burning’ fat.
In order to best treat this issue, researchers have found that there is a nerve that signals molecules called neuropeptide Y (NPY) as a response to starvation, which increases one’s food intake and lessens the output of energy.
This study, which was done in mice, saw how a drug managed to block a receptor for NPY while also increasing the heat generation in the fat tissue. For the animals that were fed high-fat diets, the drug managed to lower their weight gain by around 40%. While the drug also didn’t appear to cross the blood-brain barrier, unlike other weight loss drugs do, there is also a less likely chance that it will negatively affect one’s mood either.
The World Health Organization (WHO) has shared that since 1975, the percentage of people diagnosed with obesity has more than tripled across the globe. Meanwhile in 2016, WHO also estimated that at least 39% of adults around the world will be considered overweight, with at least 13% of them being diagnosed with obesity. In addition, other health conditions are linked to obesity such as diabetes, cardiovascular disease, as well as certain cancers.
Those diagnosed with obesity can be help themselves by changing their dietary and exercise habits, which can then allow them to reach a healthy weight and maintain it as well. But a big part of the problem is that many find that moving towards a healthier lifestyle is extremely challenging for a number of reasons, which is why people have begun looking into appetite-suppressing medication as a solution for weight loss.
There are have a number of drugs that have been released over the years that work to suppress the appetite by working precisely on neurotransmitter systems in the brain. But they have been removed from the market because of their adverse effects, notably those involving heart function or moods.
The doctor that leads the neuroendocrinology group at the Garvan Institute of Medical Research in Sydney, Australia, Dr. Yanchuan Shi, says, “Most current prescribed treatments are aimed at reducing food intake by targeting the central nervous system.”
She adds, “However, these can have significant psychiatric or cardiovascular side effects, which have resulted in over 80% of these medications being withdrawn from the market.”
Dr. Shi and her colleagues, whose study has been published in Nature Communications decided to test a brand new way to lessen weight gain that doesn’t affect the central nervous system.
Preserving Energy Stores
The research team decided to focus on a single nerve signaling molecule known as NPY. What this nerve does in ‘animals’ – including rats and humans – is help them to survive in conditions that have food shortages.
The molecule NPY boosts ‘food intake and conserves energy stores by reducing heat generation in a type of fat tissue called brown adipose tissue.’ For those people that have easy access to food but don’t get enough exercise, NPY could make it harder to lose weight.
The head of the Eating Disorders Lab at the Garvan Institute, Professor Herbert Herzog, shares, “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.”
He goes on to say, “Today, however, these advantageous effects can exacerbate existing diet-induced weight gain, leading to obesity and metabolic disease.”
Dr. Shi, Professor Herzog and their other colleagues decided to look into the effects of a drug named BIBO3304 on mice and on human fat cells from participants with obesity. What the research group found was that the drug managed to block YA, which is a type of cell receptor for NPY that’s found in the fat tissue and other tissues within the body.
Notably, BIBO3304 didn’t manage to cross the blood-brain barrier, which means that it is also unlikely to cause any adverse moods either.
Heightened Heat Generation
With or without BIBO3304, the researchers feed mice a high-fat diet for seven weeks.
What they discovered was that the mice that were given the drug gained up to 40% less weight than those that didn’t take the drug. According to the team, they figured out that this was due to an increased heat generation in the animals’ brown adipose tissue, as well as a reduced fat mass overall.
Dr. Shi explains, “The Y1 receptor acts as a ‘brake’ for heat generation in the body. In our study, we found that blocking this receptor in fat tissues transformed the ‘energy-storing’ fat into ‘energy-burning’ fat, which switched on heat production and reduced weight gain.”
Moreover, they also found out that the fat tissue from both mice and humans diagnosed with obesity actually had higher gene activities for the Y1 receptor than the tissue that was taken from those considered to have a “healthy weight.”
The researchers iterated that this could be a possible explanation as to why losing weight can be so hard, ‘given that NPY increases food intake and reduces energy output when it binds to Y1.’
When the group applied the BIBO3304 drug to their fat cells sample taken from those with obesity, the cells turned on the same genes that were involved in heat generation as those that were seen activated in the mice as well.
The researchers hypothesize that possibly the drug, or other similar molecules, could possibly work the same in humans as it does in mice.
What Are the Other Added Benefits?
Aside from lessening any weight gain the mice, the study authors also found out that by blocking Y1, there are a number of add on benefits, such as glucose metabolism improvement. They note that as the Y1 contracts blood vessels, using BIBO3304 to block the Y1, it might just open the blood vessels more, which then lower blood pressure, the process of which is called vasodilation.
Dr. Shi told the publication MNT, “We predict that blocking this receptor could cause vasodilation that may be beneficial in the context of hypertension, but further study needs to be done to confirm this.”
The researchers also explained earlier how BIBO3304 managed to stimulate bone growth. This in turn will aid in keeping bone density and preventing osteoporosis in older adults.
However, Dr. Shi also noted that the study didn’t test directly if the drug does cause weight loss in those with obesity. Instead, the study showed how BIBO3304 managed to counter weight gain in mice.
Dr. Shi shares, “While we didn’t test the approach in models of obesity, obesity is, similarly, a condition of energy oversupply due to the accumulation of fat. Therefore, our study suggests that a treatment like BIBO3304 could help treat obesity by increasing energy expenditure through the burning of fat, leading to weight loss.”
Meanwhile, emeritus professor of human metabolism at the University of Oxford in the UK, Keith Frayn, also shared with MNT that mice and humans have very different metabolisms.
He said, “I don’t place a lot of weight on studies in small rodents, especially in this field. Small rodents have a much greater capacity than do humans for up-regulating thermogenesis [increasing their heat generation]. So we cannot assume that these studies in mice will translate to humans until they are tested.”
But it’s almost safe to say that many will be waiting for the day when these human trials either prove or negate whether BIBO3304 will do the same for humans as it does for their tiny white furry friends.
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