Go to
JCI Insight
Abstract
WNT signaling plays a central role in the regulation of cellular growth and differentiation. In this issue of the JCI, Mori et al. link WNT signaling to the oxidative capacity of adipocytes during obesity. They show that secreted frizzled-related protein 5 is an extracellular matrix–residing protein that is highly induced during obesity and inhibits oxidative phosphorylation in a tissue-autonomous manner, possibly by sequestering WNT3a. These results implicate local WNT signaling as an attractive target for combating obesity.
Authors
Alexander Rauch, Susanne Mandrup
Figure 1
SFRP5 is an adipocyte-derived, matrix-residing protein that sequesters WNTs to reduce WNT signaling.
Options:
View larger image
(or click on image)
Download as PowerPoint
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 (Sfrp5Q27stop ), adipocytes keep their oxidative potential, which leads to an overall shift to smaller adipocytes and thus limits weight gain. FZ-R, frizzled receptor.
Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)