Cationic Nanomaterials Might Inhibit the Unhealthy Storage of Enlarged Fat Cells: Study

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According to a study published in Science Daily, obesity-related illnesses such as hypertension, diabetes, chronic inflammation, and cardiovascular disease have been actively researched for quite some time. Smoking, excessive alcohol use, and obesity have all been linked to increased cancer risk, and other studies have supported these findings.  

Fat cells, which develop from a small fibroblast-like progenitor, not only grow by accumulating lipids but also activate the genes required for fat cell proliferation and differentiation (adipocytes and adipose tissue). Fat cells have no other job but to store fat. However, if fat cells collect excessive lipids, the health problems associated with obesity may be aggravated.  

Many people would benefit significantly if we could safely target fat cells and decouple deficient fat synthesis from good fat metabolism. It has been challenging to develop depot-specific medicines for obesity because fat tissue does not accumulate in one continuous mass but in isolated areas (depots).  

As opposed to the more dangerous visceral fat surrounding the digestive organs, subcutaneous fat is prevalent throughout the body and does not offer as much of a health concern. A bulging stomach is caused by visceral fat, whereas jowls, flabby arms, and other places are caused by subcutaneous fat.

There is currently no technology to directly target and eliminate visceral fat. Liposuction and other existing fat removal treatments are invasive and frequently result in permanent scars.  

Cationic nanoparticles have been used in recent investigations to target fat cells. Thanks to two recent studies, scientists from Columbia University’s Engineering and Irving Medical Center (CUIMC) may have uncovered a way to safely and effectively target fat cells in specific depots. These findings suggest a novel approach to treating obesity by employing cationic nanoparticles to target fat and selectively limit harmful adipose tissue formation.

These materials rearrange fatty tissue rather than remove it, as liposuction does. The first study, published recently in Nature Nanotechnology, focuses on the problem of abdominal fat, sometimes known as visceral adiposity. The second research, which looked at inflammation and subcutaneous fat in adults with chronic obesity, was published online on November 28 by Biomaterials.  

Adipose tissue contains high concentrations of negatively charged extracellular matrix (ECM) to bind fat cells together, according to a team of scientists led by CUIMC’s Li Qiang, associate professor of pathology and cell biology, and Kam Leong, Samuel Y. Sheng Professor of Biomedical Engineering and Systems Biology.   

They hypothesized that the negatively charged ECM might act as a conduit for positively charged compounds. Obese mice were cured using PAMAM generation 3 (P-G3), a positively charged nanomaterial. Because P-G3 traveled swiftly throughout the tissue, scientists were relieved to learn that their aim to lower visceral fat had worked.  

The P-G3-treated mice then lost weight because the fat storage mechanism in their fat cells was disrupted. This was surprising because P-established G3 has been shown to decrease inflammation by neutralizing negatively charged pathogens such as DNA/RNA cell debris.  

“Our strategy is unique—it distinguishes it from pharmaceutical or surgical therapy,” says Qiang, an expert in obesity and adipocyte biology. “Reviving healthy fat cells with cationic charge is a revolutionary way to treat obesity. This unique method, in my opinion, will allow for efficient and healthy fat loss.”  

P-G3 encourages forming new adipose tissue cells while inhibiting the expansion of existing fatty tissue cells, which is both good. These two experiments show that the cationic chemical P-G3 has fascinating effects on fat cells, including its involvement in encouraging the production of new fat cells and its capacity to decouple lipid storage from fat cell housekeeping.

Mice increased the healthy, little fat cells (adipocytes) observed in babies and top athletes, which defend against hazardous lipid buildup. The discovery of P-G3 uncoupling activity in human fat biopsies implies that it might be used therapeutically.  

“With P-G3, fat cells may still be fat cells, but they can’t grow up,” said polycation proponent Leong. “Our findings highlight an unexpected technique for reducing visceral fat and give a fresh tool to examine cationic nanoparticles for treating metabolic illnesses,” the researchers write.  

Leong and Qiang hope their newly discovered ability to target visceral fat will have various uses. Biomaterials research has shown that P-G3 may be injected locally into a particular subcutaneous fat depot, similar to Botox. P-G3 is now being modified by chemists working on pending patents to increase its effectiveness, safety, and depot specificity.  

Scientists are particularly enthusiastic about the prospect of using P-G3 to deliver medications and gene treatments to specific fat depots. Thiazolidinediones (TZDs) are a solid but dangerous medicine used to treat type 2 diabetes that has been related to heart failure and is now prohibited in several countries. This discovery has the potential to repurpose numerous drugs that have been declared harmful due to systemic safety issues.  

“We are quite delighted to learn that cationic charge is the key to precisely targeting fat tissue,” said Qiang. “We can now target a specific depot anywhere on the body to eliminate fat without risking cell death. This is a huge accomplishment in the fight against obesity.” 

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