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Signals from Body Fat to Other Organs—Small Packages with Big Metabolic Impact

Researchers discovered a way that fat tissue regulates metabolism—it produces a variety of tiny but powerful molecules, called miRNAs (or microRNAs), and sends these out through the bloodstream to control biological processes elsewhere in the body. Previous studies had shown that fat tissue also releases hormones with far-ranging effects. The new discoveries thus add miRNAs to the metabolic toolbox of fat.

The researchers investigated miRNAs from fat tissue because past studies had illuminated their importance in cells throughout the body; and altered levels of miRNAs had been observed in obesity, diabetes, and another condition, lipodystrophy, associated with abnormalities in body fat. To gain new insights, the researchers began by comparing normal male mice to male mice that were deficient in miRNA production in fat tissue (but not elsewhere), to see whether this deficiency affected miRNAs in the blood. In the bloodstream, miRNAs often travel in small packages called exosomes, and the researchers found that levels of hundreds of different types of miRNAs were reduced in exosomes from the mice deficient in fat-derived miRNAs. These mice also had metabolic problems, including impaired blood glucose (sugar) regulation. When the researchers transplanted fat tissue, particularly the type known as brown fat tissue, from normal mice into the miRNA-deficient mice, they found partial restoration of miRNAs in the blood and improvement in glucose levels. These results demonstrated that normal fat tissue is a key source of circulating miRNAs, with effects on health. Other experiments also showed that fat deploys miRNAs to control metabolism from afar. For these experiments, the researchers drew upon knowledge that miRNAs block the flow of information encoded by various genes, so that the information cannot be used to make proteins. They found that miRNA-containing exosomes from mouse fat tissue travel to the liver and regulate a gene there, reducing levels of the protein it encodes.

The researchers also studied miRNAs in blood samples from human volunteers, including healthy individuals and people with lipodystrophy, a condition marked by loss of body fat where it should be, accumulation of fat where it can be toxic, and increased risk for diabetes. The levels of many miRNAs were lower in people with lipodystrophy than in healthy people, a sign that normal fat tissue is a source of circulating miRNAs in humans.

This study highlights a role for miRNAs in the regulation of metabolism by body fat. With further research, scientists may be able to develop interventions that target fat-derived miRNAs to improve health.

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