Innovative technique converts white fat to brown fat

Brown fat tissue in the body can burn enormous amounts of energy to generate heat, and studies in humans and animals have suggested that increasing the amount of healthy brown fat might help weight management and reduce symptoms of diabetes. However, how to safely and effectively increase brown fat has been a significant challenge for researchers.

A Columbia Engineering team led by Sam Sia, professor of biomedical engineering, has developed a simple, innovative method to directly convert white fat to brown fat outside the body and then reimplant it in a patient. The technique uses fat-grafting procedures commonly performed by plastic surgeons, in which fat is harvested from under the skin and then retransplanted into the same patient for cosmetic or reconstructive purposes. The researchers report in a Scientific Reports study (May 21) that they successfully converted harvested white fat to brown fat in the lab for potential use as a therapy.

Other methods to increase brown fat include chronic cold exposure, which is uncomfortable for most people, and pharmaceuticals that can cause side effects by targeting other organs. "Our approach to increasing brown fat is potentially safer than drugs because the only thing going into patients is their own tissue, and it's highly controllable because we can tune the amount of brown fat we inject," says Sia. "The process is also so simple that it could be potentially performed using an automated system within a doctor's office or clinic."

The team converted white fat to brown fat by culturing tissue fragments in media containing growth factors and other endogenous browning factors for one to three weeks to stimulate the "browning" process. They assessed the browning of the white fat by measuring levels of several brown fat biomarkers, including mitochondrial activity and the brown fat protein marker UCP1. In one of the study's experiments, they discovered that subcutaneous white fat in mice could be directly converted to brown fat outside the body, and that the brown fat both survived and remained stable after injection into the same mouse for a long period (two months in this experiment).

"The persistence of the converted brown fat is very important because we know that when white fat is naturally stimulated to turn to brown fat in vivo, through cold exposure for example, it can rapidly change back when the stimulation is removed," says Brian Gillette, the study's co-author and a Columbia-trained biomedical engineer now working in the department of surgery at NYU Winthrop Hospital. "Even though we could repeat the procedure several times if we needed to, since it's minimally invasive, it is critical that the brown fat survives well and remains stable so that it can function as an effective therapy."

The researchers then used their methods on human subcutaneous fat and were able to effectively convert it to brown fat. "This suggests that it might be possible one day to attempt our approach in humans as a potential therapy to help with weight loss, control of blood glucose levels, or to prevent weight gain," says Nicole Blumenfeld, a PhD student working with Sia and lead author of the paper.

The researchers note that, while the mice on a high fat diet treated with directly converted brown fat in the experiment did not show statistically significant weight loss versus a control group treated with unconverted white fat, the study demonstrates a simple and scalable tissue-grafting strategy that increases endogenous brown fat.

"This is an exciting advance toward engineered brown adipose tissue in clinical applications if it is proven to be safe and effective in humans," says Li Qiang, assistant professor in pathology and cell biology at Columbia University Medical Center who was not involved with this study. An expert in the pathophysiology of diabetes and obesity, Qiang documented the mechanism that promotes the "browning" of white adipose tissue.

The researchers are now refining their techniques and dosages and running further studies on the impact of their methods on metabolism and weight regulation. "There is a clear need to explore new weight-loss approaches with the potential for low rates of complications and long-term efficacy," Sia adds. "The ability to culture large quantities of tissue at once while retaining its 3D vascular structure is advantageous and holds promise as a potential approach in clinical weight management."

Nicole R Blumenfeld, Hwan June Kang, Anna Fenzl, Ziwei Song, Janice J Chung, Ranjodh Singh, Roshawn Johnson, Ayse Karakecili, Jun B Feranil, Ninna S Rossen, Vivian Zhang, Sahir Jaggi, Bret McCarty, Steven Bessler, Gary J Schwartz, Robert Grant, Judith Korner, Florian W Kiefer, Brian M Gillette, Samuel K Sia.
A direct tissue-grafting approach to increasing endogenous brown fat.
Scientific Reportsvolume 8, Article number: 7957 (2018). doi: 10.1038/s41598-018-25866-y.

Most Popular Now

Regorafenib to be tested in brain cancer patients …

Bayer announced that the regorafenib arm of the platform trial "GBM AGILE" (Glioblastoma Adaptive Global Innovative Learning Environment) opened for enrollment in the US ...

Sanofi and Google to develop new healthcare Innova…

Sanofi and Google will establish a new virtual Innovation Lab with the ambition to radically transform how future medicines and health services are delivered by tapping i...

Bristol-Myers Squibb provides update on pending me…

Bristol-Myers Squibb Company (NYSE: BMY) today provided an update on the approval process and timeline for the Company’s pending merger with Celgene Corporation (NASDAQ: ...

Japan becomes the first country to approve Roche's…

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Rozlytrek® (entrectinib) for the treatment of a...

Breztri Aerosphere (PT010) approved in Japan for p…

AstraZeneca announced that Breztri Aerosphere (budesonide/glycopyrronium/ formoterol fumarate), formerly PT010, has been approved in Japan as a triple-combination therapy...

FDA approves Amgen and Allergan's KANJINTITM (tras…

Amgen (NASDAQ:AMGN) and Allergan plc (NYSE:AGN) announced that the U.S. Food and Drug Administration (FDA) has approved KANJINTITM (trastuzumab-anns) for all approved ind...

Vitamin D may not help your heart

While previous research has suggested a link between low levels of vitamin D in the blood and an increased risk of cardiovascular disease, a new Michigan State University...

Human-on-a-chip model tests cancer drug efficacy a…

A reconfigurable "body-on-a-chip" model could transform drug development by simultaneously measuring compound efficacy and toxicity, for both target cells and other organ...

Pathogen engineered to self-destruct underlies can…

A team of investigators has developed a cancer vaccine technology using live, attenuated pathogens as vectors. A feature of the vaccine causes these bacteria to self-dest...

Artificial DNA can control release of active ingre…

A drug with three active ingredients that are released in sequence at specific times: Thanks to the work of a team at the Technical University of Munich (TUM), what was o...

How gastric stem cells fight bacteria

Stem cells are not only key players in tissue regeneration, they are also capable of taking direct action against bacteria. This is the finding of a study conducted by re...

Researchers identify enzyme that suppresses immune…

Immunotherapies have transformed cancer care, but their successes have been limited for reasons that are both complex and perplexing. In breast cancer especially, only a ...