Major obesity advance takes out targeted fat depots anywhere in the body and restores healthier metabolic function

Very good news! I am glad to report today another possibly major breakthrough!

"... Scientists are reporting an exciting advance in this field, demonstrating how positively-charged nanomaterials can be injected into unhealthy fat to return it to a healthy state, laying the foundation for treatments that selectively target fat depots anywhere in the body. ...

The research team set out to remodel these fat cells rather than simply destroy them, and have found success using a positively charged nanomaterial called PAMAM generation 3 (P-G3). The scientists were inspired to deploy P-G3 against fat cells after finding that some fat tissue contains a negatively charged extracellular matrix (ECM), the support structure for the cells. This raised the possibility that the ECM could act as a transport system for positively charged molecules.

So, the team injected P-G3 into obese mice and indeed found that it spread rapidly throughout the fat tissue. They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result. ..."

"... Two new studies from researchers ... may have the answer to targeting fat cells depot-specifically and healthily. The papers demonstrate a new method to treat obesity by using cationic nanomaterials that can target specific areas of fat and inhibit the unhealthy storage of enlarged fat cells. The materials remodel fat rather than destroying it, as, for example,  liposuction does.

The first paper ... focuses on visceral adiposity, or belly fat.
The second paper ... focuses on fat underneath the skin as well as chronic inflammation associated with obesity.

The team of researchers ... recognized that adipose tissue contains large amounts of negatively charged extracellular matrix (ECM) to hold fat cells. They thought that this negatively charged ECM network might provide a highway system of sorts for positively charged molecules. So they took a positively charged nanomaterial, PAMAM generation 3 (P-G3), and injected it into obese mice. The P-G3 quickly spread throughout the tissue and the team was excited that their method to specifically target visceral fat worked.
And then something intriguing happened: P-G3 shut off the lipid storage program in fat cells and the mice lost weight. This was totally unexpected, given the well-established function of P-G3 in neutralizing negatively charged pathogens, such as DNA/RNA cell debris, to alleviate inflammation. ..."

From the abstract of the first study:

"... Here we develop a polycation-based nanomedicine polyamidoamine generation 3 (P-G3) that—when delivered intraperitoneally—selectively targets visceral fat due to its high charge density. Moreover, P-G3 treatment of obese mice inhibits visceral adiposity, increases energy expenditure, prevents obesity and alleviates the associated metabolic dysfunctions. In vitro adipogenesis models and single-cell RNA sequencing revealed that P-G3 uncouples adipocyte lipid synthesis and storage from adipocyte development to create adipocytes that possess normal functions but are deficient in hypertrophic growth, at least through synergistically modulating nutrient-sensing signalling pathways. The visceral fat distribution of P-G3 is enhanced by modifying P-G3 with cholesterol to form lipophilic nanoparticles, which is effective in treating obesity. Our study highlights a strategy to target visceral adiposity and suggests that cationic nanomaterials could be exploited for treating metabolic diseases."

From the abstract of the second study:

"... Here, we report that polycationic polyamidoamine (PAMAM) treatment can improve both aspects of obesity. With the discovery that the plasma cell-free RNA (cfRNA) level is elevated in obese subjects, we applied the cationic PAMAM generation 3 (P-G3) scavenger to treat diet-induced obese (DIO) mice. Intraperitoneal delivery of P-G3 alleviated the chronic inflammation in DIO mice and reduced their body weight, resulting in improved metabolic functions. To further enhance the applicability of P-G3, we complexed P-G3 with human serum albumin (HSA) to attain a sustained release, which showed consistent benefits in treating DIO mice. Local injection of HSA-PG3 into subcutaneous fat completely restricted the distribution of the complex within the targeted depot and reduced focal adiposity. ..."

Major obesity advance takes out targeted fat depots anywhere in the body

Positively Charged Nanomaterials Treat Obesity Anywhere You Want Columbia researchers discover that the cationic charged P-G3 reduces fat at targeted locations by inhibiting the unhealthy lipid storage of enlarged fat cells

Selective targeting of visceral adiposity by polycation nanomedicine (open access)

Polycationic PAMAM ameliorates obesity-associated chronic inflammation and focal adiposity (no public access)

Graphical abstract

Fig. 1: P-G3 is selectively distributed to visceral fat.