Aldehydes alter TGF-β signaling and induce obesity and cancer.

ABSTRACT: Obesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)-affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2^-/- and Aldh2^-/-Sptbn1^+/- mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). Mechanistic studies demonstrate aberrant transforming growth factor β (TGF-β) signaling through 4-HNE modification of th

SUBMITTER: Yang X 

PROVIDER: S-EPMC11560041 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature