Activating PIK3CA mutation promotes overgrowth of adipose tissue via inhibiting lipophagy in macrodactyly.

ABSTRACT: Excessive proliferation and lipid accumulation of adipose tissue are the main pathological alterations in macrodactyly. Our previous studies found that macrodactyly exhibits abnormal lipid metabolism and inhibited autophagy, but the underlying mechanisms remain unclear. This study aims to investigate the regulatory mechanisms of autophagy in macrodactyly. The therapeutic impact and underlying mechanisms of autophagy on lipid accumulation, induced by a gain-of-function mutation of PIK3CA in macrodactyly, were assessed with respect to autophagy, lipid metabolism, oxidative stress, and deubiquitination. Autophagy deficiency resulting from PIK3CA mutation in macrodactyly led to excessive accumulation of adipose tissue. Lipid accumulation can be mitigated by inducing lipophagy of lipid droplets

SUBMITTER: Yin Y 

PROVIDER: S-EPMC12501352 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature