Tag Archives: metabolic disorders

Melting body fat with a microneedle patch

For many people this may seem like a dream come true but there is a proviso. So far researchers have gotten to the in vivo testing (mice)  with no word about human clinical trials, which means it could be quite a while, assuming human clinical trials go well, before any product comes to market. With that in mind, here’s more from a Sept.15, 2017 news item on Nanowerk,

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders like obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

A Sept. 15, 2017 Columbia University Medical Center news release on EurekAlert, which originated the news item, describes the research further,

Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat–a process named browning–which can happen naturally when the body is exposed to cold temperatures–as a treatment for obesity and diabetes.

“There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology and cell biology at CUMC. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.”

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter–too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

“The nanoparticles were designed to effectively hold the drug and then gradually collapse, releasing it into nearby tissue in a sustained way instead of spreading the drug throughout the body quickly,” said patch designer and study co-leader Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The new treatment approach was tested in obese mice by loading the nanoparticles with one of two compounds known to promote browning: rosiglitazone (Avandia) or beta-adrenergic receptor agonist (CL 316243) that works well in mice but not in humans. Each mouse was given two patches–one loaded with drug-containing nanoparticles and another without drug–that were placed on either side of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were also given two empty patches.

Mice treated with either of the two drugs had a 20 percent reduction in fat on the treated side compared to the untreated side. They also had significantly lower fasting blood glucose levels than untreated mice.

Tests in normal, lean mice revealed that treatment with either of the two drugs increased the animals’ oxygen consumption (a measure of overall metabolic activity) by about 20 percent compared to untreated controls.

Genetic analyses revealed that the treated side contained more genes associated with brown fat than on the untreated side, suggesting that the observed metabolic changes and fat reduction were due to an increase in browning in the treated mice.

“Many people will no doubt be excited to learn that we may be able to offer a noninvasive alternative to liposuction for reducing love handles,” says Dr. Qiang. “What’s much more important is that our patch may provide a safe and effective means of treating obesity and related metabolic disorders such as diabetes.” [emphasis mine]

The patch has not been tested in humans. The researchers are currently studying which drugs, or combination of drugs, work best to promote localized browning and increase overall metabolism.

The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health (1UL1TR001111, R00DK97455, and P30DK063608).

Notice the emphasis on health and that the funding does not seem to be from industry (the National Institutes of Health is definitely a federal US agency but I’m not familiar with the North Carolina Translational and Clinical Sciences Institute).

Getting back to the research, here’s an animation featuring the work,

Here’s a link and a citation for the paper,

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment by Yuqi Zhang†, Qiongming Liu, Jicheng Yu†, Shuangjiang Yu, Jinqiang Wang, Li Qiang, and Zhen Gu. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b04348 Publication Date (Web): September 15, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

I would imagine that Qiang and his colleagues will find a number of business entities will be lining up to fund their work. While the researchers may be focused primarily on health issues, I imagine business types will be seeing dollar signs (very big ones with many zeroes).

Could engineered nanoparticles be behind rise in obesity and metabolic disorders?

The researchers haven’t published a study and they have used fruit flies as their testing mechanism (animal models) so, it’s a little difficult (futile) to analyze the work at this stage but it is intriguing. A June 9, 2015 news item on Azonano announces a research collaboration  designed to examine the impact engineered nanoparticles have on the gut and the gut microbiome,

Researchers at Binghamton University believe understanding nano particles’ ability to influence our metabolic processing may be integral to mediating metabolic disorders and obesity, both of which are on the rise and have been linked to processed foods.

Anthony Fiumera, associate professor of biological sciences, and Gretchen Mahler, assistant professor of biomedical engineering, are collaborating on a research project funded by a Binghamton University Transdisciplinary Areas of Excellence (TAE) grant to discover the role ingested nanoparticles play in the physiology and function of the gut and gut microbiome.

A June 8, 2015 Binghamton University news release, which originated the news item, describes the reasoning behind the research,

The gut microbiome is the population of microbes living within the human intestine, consisting of tens of trillions of microorganisms (including at least 1,000 different species of known bacteria). Nanoparticles, which are often added to processed foods to enhance texture and color, have been linked to changes in gut function. As processed foods become more common elements of our diet, there has been a significant increase in concentrations of these particles found in the human body.

Fiumera works in vivo with fruit flies while Mahler works in vitro using a 3-D cell-culture model of the gastrointestinal (GI) tract to understand how ingesting nanoparticles influences glucose processing and the gut microbiome. By using complementary research methods, the researchers have helped advance each other’s understanding of nanoparticles.

Using fruit flies, Fiumera looks at the effects of nanoparticles on development, physiology and biochemical composition, as well as the microbial community in the GI tract of the fly. The fly model offers two advantages: 1) research can be done on a wide range of traits that might be altered by changes in metabolism and 2) the metabolic processes within the fly are similar to those in humans. Fiumera also aims to investigate which genes are associated with responses to the nanoparticles, which ultimately may help us understand why individuals react differently to nanoparticles.

For this project, Mahler expanded her GI tract model to include a commensal intestinal bacterial species and used the model to determine a more detailed mechanism of the role of nanoparticle exposure on gut bacteria and intestinal function. Early results have shown that nanoparticle ingestion alters glucose absorption, and that the presence of beneficial gut bacteria eliminates these effects.

Mahler was already investigating nanoparticles when she reached out to Fiumera and proposed they combine their respective expertise. With the help of undergraduate students Gabriella Shull and John Fountain and graduate student Jonathan Richter, Fiumera and Mahler have begun to uncover some effects of ingesting nanoparticles. Since they are using realistic, low concentrations of nanoparticles, the effects are slight, but eventually may be additive.

The most interesting aspect of this research (to me) is the notion that the impact may be additive. In short, you might be able to tolerate a few more nanoparticles in your gut but as more engineered nanoparticles become part of our food and drink (including water) and your gut receives more and more that tolerance may no longer possible.

There is increasing concern about engineered nanoparticles as they cycle through environment and the US Environmental Protection Agency (EPA) funded a programed by Arizona State University (ASU), LCnano Network (part of the EPA’s larger Life Cycle of Nanomaterials project). You can find out more about the ASU program in my April 8, 2014 post (scroll down about 50% of the way).

Getting back to Binghamton, I look forward to hearing more about the research as it progresses.