Obesity has reached unprecedented levels worldwide. Characterized by an excess of body fat, this complex and multi-faceted condition not only poses immediate health risks but also serves as a precursor to a myriad of chronic diseases, such as type II diabetes and cardiovascular diseases.
In the pursuit of effective interventions, scientists are trying to find new solutions to address this urgent public health issue. As an example, in the last few weeks, a new drug has been approved in the United States to address weight loss in obese and overweight people by promoting decreased appetite, adding to similar drugs already on the market.
Although effective in many cases, these therapies come with risks, like pancreatitis and kidney failure, as was shown in 0.2% (3 of 1306 patients) of people analyzed in clinical trials of semaglutide, a drug that is used in several formulations for the treatment of type 2 diabetes and obesity, tested in this case for weight management. Moreover, due to the immense number of people willing to take these therapies, companies are failing to supply a growing market.
“There is an urgent imperative to develop obesity treatment strategies with higher efficacy and minimized toxicity,” said Leilei Shi, a researcher at the Sun Yat-Sen University in Shangai, China.
In a recent study published in Small, Shi, together with a group of researchers, unveiled a novel approach to combating obesity via a nanotechnology that could help eliminate excess fat from the body.
A combined approach to tackle weight loss
In the human body there are two types of adipose tissue, commonly known as body fat: white and brown. While white adipose tissue is primarily responsible for energy storage, brown is actively engaged in metabolic processes and plays a role in heat production.
Current approaches to eliminating excess white adipose tissue are generally invasive, like gastric bypass surgery, gastric banding, and liposuction.
Shi and her collaborators therefore aimed to develop a new technology to address excess body fat with minimal undesired side effects using nanoparticles that incorporated two techniques currently in independent development.
The first technique is photodynamic therapy, which uses light-sensitive molecules to generate reactive oxygen species to kill fat cells. The second is adipose browning induction, where white adipose tissue acquires characteristics of brown adipose tissue. Typically, this process is achieved through interventions like exposure to cold temperatures or specific medications targeting signaling pathways. However, these methods are generally slow.
To build their adipose-targeting nanoparticles, Shi and her team incorporated a peptide that binds to the surface of white adipose cells, to guide the nanoparticles to the tissue of interest, an agent called protoporphyrin IX and iron ions to facilitate the photodynamic therapy.
The fourth component they included was baicalin, a molecule that activates a key protein in the fatty acid metabolism to transform white adipose tissue into fat-burning brown tissue, a process known as browning.
Shi explained that, to her knowledge, there are no similar therapies in the clinic so far, but positive early experimental results provide promising support for advancing its development. In cell lines, observing when the nanoparticles entered the cytoplasm of white adipose cells and how upon laser illumination, oxygen was generated, indicating the nanoparticle’s photodynamic therapy element was activated.
Later, with molecular techniques, the scientists were able to identify that cultured white adipose cells treated with the nanoparticles started producing a higher quantity of proteins related to the mechanism of energy expenditure, suggesting that the cells were in the process of transforming into brown adipose cells.
The therapy was then tested in obese mice, where after two injections per week followed by a laser irradiation for five minutes post-injection, repeating the procedure for eight weeks, the treated animals showed a leaner body shape with reduced white adipose tissue and lower body weight compared to control animals that did not receive the treatment.
A promising first step
Shi says she remains confident that this combined nanoparticle therapy has potential, but there are still hurdles and many more tests to run before it can be applied in a clinical setting. “We will try to develop more efficient and safer [light-activated molecules that produce reactive oxygen species after light irradiation] and natural active products,” she added.
“The experimental design is innovative and tries to address a problem as serious as obesity [but] additional in vivo measurements should be addressed,” said Ana Alzamendi, a researcher at the Laboratory of Neuroendocrinology at the IMBICE in La Plata, Argentina, where she studies the physiology of white adipose tissue and how it controls the energy homeostasis of the organism. Alzamendi was not involved in the current study.
“[Although] the translational potential of this technique in humans should be considered as promising, obesity is a multifactorial disease, thus, the possibility of developing a treatment must be taken seriously, considering many physiological factors, and not only [white] adipose tissue excess,” she continued.
This novel nanotherapy could therefore be incorporated into a multifaceted treatment strategy directed towards individuals grappling with severe health implications of obesity.
“Obesity is a serious health problem worldwide, and people tend to think that ‘magic results’ will be available at any moment,” said Alzamendi. “Both the scientific community and communicators must have the obligation to report scientific progress responsibly and clearly, with the aim of not generating false expectations in those suffering this disease or to the general public.”
Reference: Chuan Ma, et. al., Adipose Tissue Targeting Ultra-Small Hybrid Nanoparticles for Synergistic Photodynamic Therapy and Browning Induction in Obesity Treatment, Small (2023). DOI:10.1002/smll.202308962
Feature image credit: charlesdeluvio on Unsplash
