Brown from white
Obesity is the main cause of type 2 diabetes and related chronic diseases. Scientists from the Joslin Diabetes Center, USA, have presented proof of concept for a new cell therapy for this condition. They created brown fat-like cells (human brown-like, HUMBLE) by genetically modifying human white fat cells.
Brown fat cells burn energy, not accumulate it like white fat cells. Brown fat is able to reduce elevated levels of glucose and lipids in the blood associated with diabetes and other metabolic diseases. Overweight or obese people tend to have a lower percentage of brown fat.
The researchers created HUMBLE cells from the precursors of human white fat cells. To do this, they used the CRISPR-Cas9 genome editing system to enhance the expression of the UCP1 gene, which forces the precursors of white fat cells to develop into cells similar to brown fat cells.
Transplanted into mice deprived of the immune system, the HUMBLE progenitor cells turned into cells that functioned as the mice's own brown fat cells.
The team compared HUMBLE cells with the original white fat cells in mice that received a high-fat feed. Mice that received HUMBLE showed much greater sensitivity to insulin and the ability to absorb glucose from the blood – two key factors impaired in type 2 diabetes.
In addition, mice with HUMBLE cells gained less weight than mice with transplanted white fat cells, remaining in the same range as animals injected with mature brown fat cells.
Researchers attribute the benefits of HUMBLE to signals from transplanted cells to mice's own brown fat cells. They secrete nitrogen monoxide, which is transferred by erythrocytes to endogenous brown cells and activates them.
If the HUMBLE method shows its effectiveness in preclinical studies, it may be possible in the future to create this type of cells for individual patients: the procedure will include the sampling of white fat cells, the isolation of progenitor cells, their modification to increase the expression of UCP1, and then the introduction of the resulting HUMBLE cells to the patient.
However, such an individual approach would be complex and expensive, so the group evaluated two other ways that might be more practical for clinical use.
One option is to use cells encapsulated in biomaterials that protect them from the attack of the patient's immune system. Researchers from the Joslin Diabetes Center have been studying such materials for cell transplantation in type 1 diabetes for a long time. Another option is gene therapy, which will increase the expression of the UCP1 gene in the precursor cells of white fat in the body, and these cells will acquire HUMBLE-like properties.
The use of cell or gene therapy for the treatment of obesity and type 2 diabetes is becoming more real. Scientific achievements, including CRISPR gene editing technologies, will help improve metabolism, normalize body weight, improve the quality of life and overall health of people with obesity and diabetes.
Article C.-H.Wang et al. CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Transplanted brown-fat-like cells hold promise for obesity and diabetes.