Figure 1. SFRP5 is an adipocyte-derived, matrix-residing protein that sequesters WNTs to reduce WNT signaling.

Endogenous WNTs stimulate the oxidative capacity of adipocytes by increasing mitochondrial number and activity. During obesity, SFRP5 levels rise, thereby suppressing the oxidative metabolism of adipocytes, which subsequently leads to adipocyte hypertrophy. In the absence of SFRP5 (Sfrp5^Q27stop), adipocytes keep their oxidative potential, which leads to an overall shift to smaller adipocytes and thus limits weight gain. FZ-R, frizzled receptor.