Researchers at the Joslin Diabetes Center have used CRISPR-Cas9 technology, known as “genetic scissors”, to convert white fat cells into brown fat cells that generate heat by burning calories.
Is gene therapy the future of the global fight against obesity and overweight?
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This is the hope of a new study by researchers from the Joslin Diabetes Center. Published in the journal Science Translational Medicine, it demonstrates the usefulness of the CRISPR-Cas9 technique, known as “genetic scissors”, to genetically transform white fat cells that store calories into brown fat cells that are easily burned to produce body heat.
“Brown fat cells burn energy instead of storing it like white fat cells,” says Yu-Hua Tseng, a researcher in the field of integrative physiology and metabolism at the Joslin Diabetes Center. In this way, brown fat cells can reduce excessive glucose and lipid levels in the blood, which are associated with metabolic diseases such as diabetes. However, overweight and obese people tend to have less of these beneficial brown fat cells. The transformed brown fat cells called HUMBLE (for “human brown-like” are supposed to overcome this problem.
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Increased insulin sensitivity
The research team first created HUMBLE cells from white preadipocytes and then used a variant of the CRISPR-Cas9 genome editing system to stimulate the expression of a gene called UCP1, which triggers the development of white preadipocytes into fat brown cells.
These HUMBLE cells were transplanted into mice without an immune system to enable their development. They then functioned as the rats’ own brown fat cells.
On a high-fat diet, the mice that received HUMBLE cells showed a much higher sensitivity to insulin and the ability to eliminate glucose from the blood than the mice in the control group. They also gained less weight.
Two options are being investigated
These preclinical results are encouraging for researchers. They hope to generate HUMBLE brown cells for individual patients soon. Such a procedure would involve taking a small number of white preadipocytes from a patient, isolating the precursor cells, modifying these cells to stimulate UCP1 expression, and then retransplanting the resulting HUMBLE cells to the patient.
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However, according to Dr. Tseng, this individualized approach can be complicated and costly. She is therefore working on alternatives. The first would be to use unadapted cells, which would then be encapsulated with biomaterials that protect the cells from rejection by the patient’s immune system. The other option is gene therapy, in which the UCP1 gene is expressed directly in the body’s white preadipocytes, giving these cells properties similar to HUMBLE.
“The use of cell or gene therapies to treat obesity or type 2 diabetes used to be science fiction. Today, scientific advances such as CRISPR will help us improve the metabolism, body weight, quality of life, and overall health of people suffering from obesity and diabetes,” Dr. Tseng concluded.
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