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New York, NY—December 1, 2022—Researchers have long been working on how to treat obesity, a serious condition that can lead to high blood pressure, diabetes, chronic inflammation and heart disease. Studies have also revealed a strong link between obesity and cancer – with recent data showing that smoking, drinking and obesity are the biggest contributors to cancer worldwide.
Developing adipose cells, which arise from a small fibroblast-like progenitor, not only activate specific genes of adipose cells but also increase them by accumulating more lipids (adipocytes and adipose tissue). In fact, lipid storage is a defining function of a fat cell. But storing too much lipid can make fat cells unhealthy and lead to obesity.
Challenges in targeting fat cells
The ability to target fat cells and safely separate unhealthy fat formation from healthy fat metabolism would be the answer to many people’s prayers. A major challenge in the treatment of obesity is that adipose tissue, which is not continuous in the body but is found fragmentarily in “depots”, has been difficult to target to precise locations in a depot-specific manner.
There are two main types of fat: visceral fat, the internal tissue that surrounds the stomach, liver and intestines, and subcutaneous fat, found under the skin anywhere in the body. Visceral fat produces potbelly; Subcutaneous fat can form chin jowls, arm fat, etc. To date, there is no way to specifically treat visceral adipose tissue. And current treatments for subcutaneous fat, such as liposuction, are invasive and destructive.
New study uses cationic nanomaterials to target fat
Two new studies from researchers at Columbia Engineering and Columbia University Irving Medical Center (CUIMC) may have the answer to specifically and healthily target fat cells. The papers demonstrate a new method for treating obesity using cationic nanomaterials that can target specific areas of fat and prevent the unhealthy storage of enlarged fat cells. The material destroys fat rather than rebuilds it, as, for example, liposuction does.
The first paper, published today by Nature Nanotechnology, focuses on visceral fat, or abdominal fat. The second paper, published online Nov. 28 by Biomaterials, focuses on fat under the skin as well as chronic inflammation associated with obesity.
The team of researchers, led by Li Qiang, Associate Professor of Pathology and Cell Biology at CUIMC, and Kam Leong, Samuel Y. Sheng Professor of Biomedical Engineering and Systems Biology at CUIMC, recognized that adipose tissue contains a large amount of negative charge extracellular. matrix (ECM) to hold the fat cells. They thought that this negatively charged ECM network might provide a kind of highway system for positively charged molecules. So they took a positively charged nano material, PAMAM generation 3 (P-G3), and injected it into obese mice. P-G3 rapidly spread throughout the tissue and the team was excited that their method of specifically targeting visceral fat worked.
unforeseen consequences
And then something intriguing happened: P-G3 turned off the lipid storage program in the fat cells, and the mice lost weight. This was completely unexpected, given the well-established function of p-G3 in neutralizing negatively charged pathogens such as DNA/RNA cell debris to reduce inflammation.
“Our approach is unique — it departs from pharmacological or surgical approaches,” says Qiang, who specializes in obesity and adipocyte biology. “We used cationic charge to rejuvenate healthy fat cells, a technique that no one has ever used to treat obesity. I think this novel strategy is the first way to reduce fat healthily and safely.” Will open the door of
P-G3 helps in the formation of new fat cells and also prevents unhealthy lipid storage of enlarged fat cells
In these two studies, the researchers found that the cationic material, P-G3, may serve an interesting function for fat cells – while it helped with new fat cell formation, it also unleashed lipid storage from the fat cells’ housekeeping functions. . And because it prevented the unhealthy lipid storage of enlarged fat cells, the mice had more metabolically healthy, younger, smaller fat cells such as those found in newborns and athletes. The researchers found that this uncoupling function of P-G3 held true in human fat biopsies, indicating translational potential in humans.
“With P-G3, fat cells can still be fat cells, but they can’t grow,” said Leong, a pioneer in using polycations to clear pathogens. “Our study uncovers an unexpected strategy for treating visceral fat and suggests a new direction of exploration of cationic nanomaterials for treating metabolic diseases.”
New applications for drug delivery, gene therapy and aesthetics
Now that they can selectively target visceral fat, Leong and Qiang envision many applications. The Biomaterials study demonstrates a simple approach that can be used for aesthetic purposes; Like Botox, P-G3 can be injected locally into a specific, subcutaneous fat depot. The investigators, who have patents pending, are now engineering P-G3 into various derivatives to improve efficacy, safety and depot specificity.
The researchers are particularly excited about developing P-G3 as a platform that can specifically deliver drugs and gene therapies to a given fat depot. This could reintroduce many drugs from systemic safety concerns, such as the thiazolidinediones (TZDs), a potent but unproven drug that is a strong modulator of adiposity and is used to treat type 2 diabetes – but has also been shown to be associated with heart failure. Has been linked to and is banned in many countries. ,
“We are very excited to find that cationic charge is the secret to targeting adipose tissue,” Qiang said. “Now we can reduce fat in a depot-specific way – anywhere we want it – and in a safe way without destroying fat cells. This is a major advance in the treatment of obesity.”
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