Researchers discovered that fat tissue releases signals called microRNAs into the bloodstream that regulate genes in another organ.
The findings suggest new ways to treat metabolism-related diseases like obesity and diabetes.
Mouse fat cells (red) and blood vessels (green).Daniela Malide, NIH National Heart, Lung, and Blood Institute
Fat tissue helps your body store excess energy. It also releases hormones and other substances that help regulate your body’s metabolism by communicating with other organs and tissues, such as your liver, pancreas, and muscles. Mammals, including people, have 2 main types of fat: white and brown. Most body fat is white fat, which stores extra energy that can then be used when needed—for example, when exercising. Whereas brown fat burns energy to help regulate body temperature.
Several cell types, including fat cells, make small pieces of genetic material, called microRNAs. The precise roles of microRNAs are currently under intense investigation. High levels of certain microRNAs have shown to correlate with the presence of several diseases, including cancer, diabetes, heart disease, and obesity.
The amount of microRNA in white fat tissue is known to decline with age. This is due to lower levels of an enzyme that processes microRNAs called Dicer. To better understand the relationship between fat cells, microRNA, and metabolism, a team led by Dr. C. Ronald Kahn of the Joslin Diabetes Center and Harvard Medical School looked at the effects of removing Dicer from both white and brown fat cells in mice. The study was supported in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results appeared on February 23, 2017, in Nature.
Removing the Dicer gene from fat cells prevented the cells from making microRNAs. Animals missing the enzyme in their fat cells had less white fat than control mice. They also had brown fat with altered properties and were insulin resistant.
The researchers measured microRNA levels in blood samples taken from both normal and genetically altered mice. Most microRNAs are found in tiny, fluid-filled sacs called exosomes. Levels of hundreds of microRNAs were significantly lower in the exosomes of mice lacking Dicer in their fat. Of these, 88% were reduced by more than 4-fold. MicroRNAs circulating in the blood outside of exosomes were also lower in the mice lacking Dicer.
People with lipodystrophy—a condition characterized by a lack of fat tissue—had low levels of circulating exosomal microRNAs as well. These results suggest that fat tissue is the main source of circulating exosomal microRNAs in the body.
The researchers transplanted fat from normal mice into mice lacking Dicer in fat tissue. They found that most microRNAs were restored to at least half of their normal levels. Brown fat transplants, but not white fat transplants, also improved the animals’ glucose metabolism.
The scientists next investigated whether microRNAs released by fat tissue could affect other tissues. Through a series of experiments, they showed that circulating exosomal microRNAs from one mouse could regulate gene expression in the liver of another.
These findings suggest that microRNAs made in fat tissue can regulate metabolism and gene expression throughout the body. Because fat is easily accessible, it might offer a way to deliver microRNAs to regulate genes in other organs.
“This mechanism may offer the potential to develop an entirely new therapeutic approach,” Kahn says.
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