The skinny on what makes us fat

Obesity is a disorder in which fat cells grow larger and accumulate. Certain proteins, called WNT family proteins, function to prevent fat cell formation. However, the activity of WNT proteins can be inhibited by secreted frizzled-related proteins (SFRPs), thus leading to fat cell generation. One of these SFRPs, SFRP5, is highly expressed during fat cell generation and increases during obesity. Dr. Ormond MacDougald and colleagues at the University of Michigan sought to determine the mechanism of SFRP5-mediated obesity and found that mice lacking SFRP5 were resistant to diet-induced obesity, despite having similar numbers of fat cells as control mice. The results from a transplantation experiment wherein fat tissue was transferred from SFRP5-deficient mice into obesity-prone mice demonstrated that the mechanism of SFRP5-mediated inhibition of fat cell generation is specific to the tissue itself and not dependent on the surrounding environment. The team also found that SFRP5-deficient mice showed increased metabolic activity compared to control mice. These findings, which were discussed in a commentary by Alexander Rauch and Susanne Mandrup at the University of Southern Denmark, shed light on the mechanism of SFRP5-mediated obesity and identify the WNT signaling pathway as a potential therapeutic target to counteract obesity.