White fat cells are the ones filled with a lipid that make up fatty deposits – and human adults have lots of them. There’s another type called brown fat cells, which we don’t have many of. They are the ones that burn and store energy. As people age or gain weight, they lose brown fat. Not much has been discovered on how the energy-burning cells can be replenished.
But now, a group of Harvard scientists has managed to turn white fat cells into energy-burning brown fat using the CRISPR gene-editing tool. The breakthrough, which helped mice on a high-fat diet stay thin and avoid diabetes, could lead to treatments for obesity-related disorders in humans.
First, the team gave human white fat cells the properties of brown fat by targeting a gene for a protein called UCP1. The gene is uniquely expressed in brown fat, and it’s the one that converts chemical energy into heat. So, the resulting cells aren’t precisely brown fat cells, but they express almost as much UCP1 as one and contain more mitochondria than white fat cells. Therefore, the researchers named them human brown-like cells – aka HUMBLE cells.
Next, the Yu-Hua Tseng led team transplanted either HUMBLE cells, white fat, or brown fat into mice. The animals were bred to have a weakened immune system so their bodies would accept the human tissue. All three groups of mice were fed the same high-fat diet.
After three months, the mice that had been given HUMBLE cells or brown fat gained significantly less weight than the ones given white fat cells. They also were more sensitive to insulin, meaning HUMBLE cells might protect against diabetes.
Mark Christian from Nottingham Trent University, who was not involved with the study, said the research could lead to other approaches to diabetes prevention and weight loss. Another discovery Tseng’s team made was that the transplanted HUMBLE cells appeared to stimulate (through chemical signaling) the mice’s existing stores of brown fat to burn more energy. Therefore, a more straightforward treatment approach (alternative to transplantation) could be to get the signal to activate the body’s brown fat reserves.
Going the transplantation route, a procedure would involve removing a small amount of the patient’s white fat, using CRISPR to engineer it into HUMBLE cells, and re-implanting it. For individuals who can’t lose weight with exercise and diet alone because of obesity and metabolic disorders, this could be a life-changing solution.
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