U.S. Department of Health and Human Services

Diet-induced Changes in Fat Tissue—Role of the FGF1 Gene and Link to Type 2 Diabetes

Scientists discovered that the FGF1 gene plays a key role in “remodelling” body fat tissue in rodents in response to dietary changes. These findings may ultimately lead to new treatments for type 2 diabetes and for reducing the elevated glucose levels often found in obese individuals. Body fat tissue typically changes to accommodate the influx of nutrients encountered following re-feeding after an overnight fast, or after a switch from a normal to a high-fat diet. In experiments to understand how these metabolic changes occur, researchers discovered that the FGF1 gene was activated in the fat tissue of mice that ate normal chow compared to those that had fasted overnight, and FGF1 induction increased even more when the mice were given a high-fat diet. The FGF1 gene was turned on by the master regulator of fat tissue, a protein called PPARγ. To gain further insights, the research team compared normal mice to those genetically engineered to lack FGF1. When allowed to eat as much as they wanted of a high-fat diet, mice lacking FGF1 gained the same amount of weight as normal mice, but otherwise their health was far worse. They developed severe type 2 diabetes; their livers were enlarged and contained excess fat; and, potentially at the root of these problems, their visceral fat tissue was abnormal. Although excess nutrients usually cause fat tissue to expand, the visceral fat of FGF1-deficient mice did not; it instead showed structural defects and more inflammation than that of normal mice. Conversely, when switching mice from a high fat diet to healthier fare, the researchers also found that FGF1 helped fat tissue adapt accordingly. These new findings suggest that FGF1 helped mitigate such problems by directing fat tissue to adjust to feeding, fasting, and—at least to some extent—a high-fat diet. Although FGF1 had been implicated in other biological processes, its crucial functions in fat tissue were initially surprising to the researchers because in previous studies, mice without FGF1 seemed perfectly fine. However, until this new study, scientists had not examined FGF1-deficient mice on a high-fat diet. The new study suggests that in mice, as in people, genetic susceptibility to type 2 diabetes and other metabolic problems may only become apparent when on an unhealthy diet, particularly one that leads to obesity. These new findings point to FGF1 as a potential target for developing novel type 2 diabetes therapies. 
 
Jonker JW, Suh JM, Atkins AR, et al. A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature 485: 391-394, 2012