Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

摘要

Mammals have different types of fat cells in their bodies. White fat cells store energy for later use, and brown and beige fat cells burn energy to help keep the body warm. Individuals who are obese typically have too many white fat cells in and around their belly. This belly fat, also called visceral fat, accumulates around the organs and is believed to contribute to metabolic diseases, such as diabetes and heart disease. Individuals who are obese also have relatively few brown and beige energy-burning fat cells. Boosting the amount of brown and beige fat in individuals who are obese has been proposed as a potential way to reduce their risk of metabolic disease. One way to do this would be to encourage white visceral fat cells to become more like energy-burning beige or brown fat cells. Recent research has shown that white fat cells contain higher amounts of a protein called Zfp423 than brown or beige fat cells. This protein turns off the genes that fat cells use to burn energy and so keeps white fat cells in an energy-storing state. Now, Hepler et al. show that genetically modifying mice to turn off the gene that produces Zfp423 specifically in the precursor cells that become white fat cells causes more energy-burning beige cells to appear in their visceral fat. The genetically modified mice were better able to tolerate cold than normal mice. When placed on a high-fat diet, the modified mice were also less likely to become resistant to the effects of the hormone insulin – a process that can lead to the development of type 2 diabetes and may be linked to heart disease. This suggests that treatments that prevent Zfp423 from working in fat cells could help to treat or prevent diabetes and heart disease in people who are obese. Before such treatments can be developed, further work is needed to investigate how Zfp423 works in more detail, and to confirm that it has the same effects in human fat cells as it does in mice.