Written By: Mayukha Kashyap
New research shows HUMBLE fat cells could help people keep weight off.
Picture Source: https://www.newscientist.com/article/2252925-body-fat-transformed-by-crispr-gene-editing-helps-mice-keep-weight-off/
Obesity stems from having excess body fat. Being obese not only affects a person’s looks; it can also be dangerous. Obesity can increase the risk of heart disease, diabetes, high blood pressure, and cancer. In fact, “obesity is the main cause of type 2 diabetes and related chronic illnesses that together will kill more people around the globe this year than the Covid-19 coronavirus” (Wang, 2020). While obesity affects more than one-third of the U.S. population, losing weight can improve health benefits. Simple actions such as dieting, increasing physical activity, and behavior changes can reduce a person’s weight. However, in some cases, people have difficulty getting rid of excess weight because of genetic predispositions. New research by Yu-Hua Tseng, a Senior Investigator in Joslin's Section on Integrative Physiology and Metabolism, suggests that transplanting HUMBLE (human brown-like) fat cells can help decrease obesity.
The human body contains both white and brown fat cells. White fat cells are predominantly used as energy storage, whereas brown fat cells burn energy. Because brown fat cells burn energy instead of storing it, they can lower glucose and lipid levels in the blood, thus reducing the risk of diabetes and other metabolic diseases. People who suffer from obesity have more white fat cells than brown fat cells; hence, their bodies tend to store fat as storage rather than burn it. HUMBLE cells were designed to overcome this barrier.
Tseng and her colleagues “used a variant of the CRISPR-Cas9 genome editing system to boost the expression of a gene called UCP1” (Joslin Diabetes Center, 2020). UCP1 is only expressed by brown fat cells and turns chemical energy into heat. After transplanting the HUMBLE cells into mice who didn’t have an immune system, they were surprised to learn that the cells developed into something resembling their brown fat cells. The HUMBLE cells expressed almost the same amounts of UCP1 as regular brown fat cells and contained more mitochondria than white fat cells.
To further test the experiment, Tseng and her colleagues injected either white fat cells, brown fat cells, or HUMBLE cells into mice without an immune system. The mice were fed a high-fat diet. For 12 weeks, the mice injected with white fat cells gained weight, while the mice injected with HUMBLE or brown fat cells gained less weight. The mice injected with HUMBLE cells were also more sensitive to insulin and cleared glucose from the blood, two reduced activities during type 2 diabetes. Scientists at the Joslin Diabetes Center discovered that the HUMBLE cells transplanted secrete nitric oxide, which activates the brown fat cells in the mice through red blood cells. This could be used for individualized patient therapy by removing trace amounts of white fat cells, converting it into brown fat cells that express UCP1, and later re-implanting them. However, Tseng believes this method is expensive and time-consuming.
One alternative Joslin Diabetes Center is pursuing is using gene therapies that express UCP1 in white fat cells to become similar to HUMBLE cells. With the help of CRISPR technology, Tseng hopes that these scientific advancements can improve a person’s metabolism, reduce weight, and improve quality of life while decreasing metabolic diseases. Though there is no cure for obesity yet, Tseng emphasizes that human trials can commence with enough research, and HUMBLE cells could be used as an alternative for people who struggle with losing weight with diet and exercise alone.
Sources:
Brett Israel, Media relations| March 6, and Brett Israel. “Brown Fat Flexes Its Muscle to
Burn Energy - and Calories.” Berkeley News, 6 Mar. 2018,
news.berkeley.edu/2018/03/06/brown-fat-flexes-its-muscle-to-burn-energy/.
Chih-Hao Wang, et al. CRISPR-engineered human brown-like adipocytes prevent
diet-induced obesity and ameliorate metabolic syndrome in mice. Science Translational
Medicine, Aug 26th, 2020 DOI: 10.1126/scitranslmed.aaz8664
Hamzelou, Jessica. “Body Fat Transformed by CRISPR Gene Editing Helps Mice Keep
Weight Off.” New Scientist, 26 Aug. 2020,
www.newscientist.com/article/2252925-body-fat-transformed-by-crispr-gene-editing-helps-
mice-keep-weight-off/.
Joslin Diabetes Center. "Transplanted brown-fat-like cells hold promise for obesity and
diabetes." ScienceDaily. ScienceDaily, 26 August 2020.
<www.sciencedaily.com/releases/2020/08/200826141413.htm>.
Mayo Clinic. “Obesity.” Mayo Clinic, Mayo Foundation for Medical Education and Research,
15 Feb. 2020,
www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742.
Comments