Recent discoveries enabling the conversion of white fat to brown fat suggest that the diseases resulting from fat will find a treatment. However, we will have to wait for the “miracle slimming treatments” – for the time being, fat conversions will only take place under the supervision of a doctor.
The first discovery was made by an international team researching the relationship between obesity and diabetes and the possibility of eliminating too much white fat (usually abdominal obesity). In addition to type 2 diabetes, scientists believe that obesity is also associated with non-genetically determined cancer, cardiovascular disease and possibly early dementia. However, until now, there has been no great opportunity to eliminate abdominal obesity that threatens health and life, and surgery alone is not always possible.
A team of scientists from the Karolinska Institutet (KI), University of Connecticut and Qingdao University, led by prof. Yihai Cao from KI stated that the distinctive feature of white fat is its relatively poor blood supply. So scientists decided to stimulate the formation of new blood vessels in white adipose tissue. This was caused by blocking the molecular receptor for the growth factor known as VEGF (R1 receptor). Mice in which it wanted to cause this effect were divided into two groups. In one group, the growth of the blood vessel network was achieved with the aid of a pharmaceutical, in the other group – through genetic modification. In both groups, the effect was the same: the expansion of the network of blood vessels resulted in an accelerated conversion of white fat into brown, and as Prof. Yihai Cao, this gives the opportunity to develop a new generation of drugs that, under medical control, will convert white fat into brown. A side effect of the research was the finding that after conversion, the tested mice increased sensitivity to insulin, which means that there is also the possibility of a new antidiabetic therapy.
A similar discovery happened to scientists from Singapore. A team of scientists from Nanyang Technological University in Singapore (NTU Singapore), led by prof. Chen Peng and prof. Xu Chenjie, dealt with the problem of non-surgical elimination of white fat deposits, which is important not only in excessive or morbid obesity, but even in the treatment of cancer. Scientists have started with a new generation of targeted drugs that make it easier to burn white fat. However, getting the drug into the body became a problem.
So the researchers created a patch containing a dose of one of two types of hormones: the Beta-3 adrenergic receptor or the T3 thyroid hormone (triiodothyronine). The patch was provided with several hundred microneedles on the inside, made of a bio-degradable substance based on corn starch. Each needle was 1,5 times thinner than a human hair. The patch was applied to the skin for just over 2 minutes to allow the microneedles to penetrate the skin. The needles degraded (dissolve) while releasing hormones into the dermis.
Both types of hormones induced an accelerated conversion of white fat to brown. In the group of mice in which the tests were carried out, the weight of fat in the body decreased by 4% within 30 weeks. and there was a rapid conversion of white fat to brown. According to scientists, this gives a chance to create a therapy in morbid and excessive obesity, as well as in diseases of the cardiovascular system. – After applying the microneedle patch to the mice, within 5 days, it began to produce brown fat from white fat, which caused an increase in energy expenditure in mice, resulting in a reduction in body fat. The amount of the drug administered to the animals per dose and body weight was much lower than the patients received orally. This reduces not only the cost of the treatment itself, but also the side effects, because the drug is released slowly – said Prof. Xu. As added by prof. Chen, the application of the patch itself is painless – the patient feels warm at the application site and this is what the needles penetrate into the skin. The slow release of the drug itself also does not cause any side effects due to the speed and similar to the natural effect of the conversion process itself.
In turn, Dr. Aung Than at the NTU School of Chemical and Biomedical Engineering performed other experiments on mice, which showed that using the patch, even when keeping the animals on a high-fat diet, reduced body fat by 30 percent. still taking place. Interestingly, the tested mice after 4 weeks showed a low level of cholesterol, with a very good lipid profile, compared to mice not subjected to such treatment. Neither were any side effects detected. The scientist used in patches a combination of the Beta-3 adrenergic receptor with hyaluronic acid, often used in cosmetic products such as masks, present naturally in human skin.
The mere use of the Beta-3 adrenergic receptor is combined in the US and Western Europe with overactive bladder treatment, while the second substance, the T3 hormone, is commonly used in the treatment of hypothyroidism. Both compounds were previously linked to possible weight loss and it was argued that they possibly contributed to the formation of brown fat. However, if it were to be administered orally for this purpose, then the doses used would have to be so high that they would cause serious side effects and would accumulate in the tissues, which would make the hormonal disorders, which are a side effect of the treatment, chronic. Hence, the mode of administration and dose for both substances is crucial to any therapeutic success. Currently, the new, tested routes of administration will be subject to Phase I clinical trials, this time in humans. It is likely that the entire clinical trial program will be shut down later this year if there are no unexpected obstacles to innovative drug use.
Literally a few days ago, the results of research by scientists from Brown University in the USA were announced. A team of scientists from this university, led by prof. Simin Liu studied the SNRK enzyme, which accelerates the metabolism and reduces inflammation in the case of fatty tissue. – Reducing inflammation in white fat, reduces the likelihood of complications such as isulin resistance, while increasing metabolism in brown fat, which means weight loss, which is important for overall health – says Prof. Simin Liu.
In the course of the research, scientists used mice that had the SNRK-coding gene turned off, and mice in which the gene was not turned off. It turned out that the mice with a knockout of the SNRK gene had a significantly higher concentration of macrophages, cells of the immune system, which are the best marker of inflammation. This meant that SNRK played a vital role in reducing inflammation in white fat. In addition, mice lacking SNRK were heavier and more fat than mice with this enzyme, importantly, their metabolism was also slower, even when administered drugs inducing faster metabolism and hence weight loss. The brown fat reserves were also lower, which proves that the metabolism was not working properly here as well.
According to Prof. Xu, further research is necessary, but it is already known that the SNRK deficiency is seriously harmful. As you can see, the issue of how to convert white fat to brown and increase metabolism does not find a very simple solution and in the future this process will certainly be conducted under the supervision of doctors.