Breakthrough Using CRISPR to Target Fat Cells in the Genetic Study of Obesity

Fat – it’s vital for life, but too much can lead to a host of health issues. Studying how fat, or fat, tissue works in the body is key to understanding obesity and other issues.

Illustration by Jill George / NIH Image Gallery – CC License

But structural differences in fat cells and their distribution throughout the body make this difficult.

“Fat cells are different from other cells in that they lack unique cell surface receptors and represent only a minority of cells in adipose tissue,” said Steven Romanelli, Ph.D., of the Department of Molecular Physiology. and integrative of the University. from Michigan.

In a new paper published in the Journal of Biological Chemistry, Romanelli, Ormand MacDougald, Ph.D., and colleagues describe a breakthrough using CRISPR-Cas9, a tool that has transformed molecular biology research, but whose use in the study of fatty tissue had been elusive.

It’s a gene-editing technique made up of an enzyme called Cas9, which can break strands of DNA, and a piece of RNA that guides the Cas9 enzyme to a specific site in the genome. for editing. The tool has been used successfully to study heart, liver, neurons and skin cells, to name a few, but never a certain type of fat cells known as brown fat. .

Using this technique, the team was able to successfully target brown fat, a specialized fatty tissue used to generate heat and protect core body temperature.

Using their adeno-associated virus CRISPR-Cas9 components, they knocked out the UCP1 gene that defines brown fat and allows it to generate heat in adult mice. They observed that the knockout mice were able to adapt to the loss of the gene and maintain their body temperature under cold conditions, hinting at other pathways involved in temperature homeostasis.

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“The biggest challenge in fat research to date has been that if you want to study gene function, you have to spend a considerable amount of time, resources and money developing a transgenic mouse” , said Romanelli.

The traditional way to develop mouse models is to breed mice with a desired mutation to delete or introduce certain genes of interest, which can take over a year and tens of thousands of dollars.

CRISPR-Cas9 has revolutionized this process.

“What we were able to do was take this whole process and distill it in two weeks to a month to generate a transgenic mouse, bringing the cost down to less than $2,000. Not only does this reduce time and cost, but it democratizes research so that any lab familiar with molecular biology techniques can adopt this method and do it themselves,” Romanelli said.

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They were also able to use this method to delete multiple genes simultaneously, which could help researchers better understand important molecular pathways.

Although these results are exploratory, this breakthrough represents an important advance in the study of fat.

(Source: Michigan Medicine, University of Michigan – by Kelly Malcom)

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