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Love Handles Get Dissolved by New Skin Patch

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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 prototype postage-sized microneedle patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders, such as obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

“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,” commented Li Qiang, Ph.D., co-study leader, who is assistant professor of pathology and cell biology at CUMC. “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.” The researchers report their developments in ACS Nano, in a paper entitled, “Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment.”

In the field of metabolic diseases, Medicilon has a portfolio of stable and effective animal models, including for Non-alcoholic Fatty Liver Disease (NAFLD), obesity and diabetes.

Obesity was classified as a “disease” by the American Medical Association in 2013. Estimates indicate that more than one third of the adult population in the U.S. is obese, and the proportion is rising. Obesity-associated disorders, including T2D, cardiovascular disease, and cancer, represent major global health threats.

Mammals have two types of fat tissue. Brown adipose tissue (BAT) burns fat to generate heat, whereas white adipose tissue (WAT) stores energy in the form of fat droplets. Adult humans have a predominance of WAT. Drugs are available that can promote the conversion of white fat into brown fat, a process termed browning, but these drugs also cause side effects. Qing noted, “… all [drugs] must be given as pills or injections. This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures.”

The researchers developed the degradable microneedle patch as an alternative treatment approach that enables localized, painless drug administration. The patches were loaded with one of two nanoparticle formulations of drugs known to promote browning—the diabetes drug rosiglitazone (Avandia®), and a beta-adrenergic receptor agonist CL 316243, which is active in mice, but not in humans and has a different mechanism of action. “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,” explained patch designer and study co-leader Zhen Gu, Ph.D., associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The team first tested the patches on normal, lean mice, to confirm sustained drug release. Analysis of fat tissues under the patches indicated shrinkage of white adipocytes and appearance of “beige” adipocytes. Gene analysis supported browning transformation of the WAT, and there was an upregulation of brown adipocyte genes. Treated mice also lost weight due to reduced fat mass and showed a 20% increase in oxygen consumption—which is a measure metabolic activity—as a result of induced browning. The team said that the calorimetric data “supported the notion that delivery of Rosi [rosiglitazone] or CL 316243 browning reagents is an efficient way to induce browning and improve metabolism.”

They then applied the rosiglitazone and CL 316243 patches to the skin of diet-induced obese mice. A fresh drug-loaded patch was placed on one side of the lower abdomen of each test mouse every three days, for four weeks. The results confirmed that both types of patch halted weight gain, which the authors say was surprising for the rosiglitazone-treated animals, as the drug can cause weight gain. Both types of patch also improved glucose clearance rate and decreased fasting blood glucose levels, indicating an improvement in insulin sensitivity. The researchers suggest that the improved glucose control was caused by the browning effect and not by the insulin-sensitizing function of rosiglitazone, as CL 316243 treatment had the same effect. Patch therapy also led to about a 30% reduction in white adipose tissue and a 20% reduction in fat pad size, with upregulation of brown adipocyte genes on the treated side.

“Our in vivo data further demonstrated systemically increase of energy expenditure and fatty acid oxidation, effective body weight control in diet-induced obese mice, as well as improved insulin sensitivity,” the authors conclude. “Taken together, our work provides a new strategy in applying drugs through MN [microneedles] as potential therapeutics for the clinical treatment of obesity and its comorbidities such as type-2 diabetes.”

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