Loss of adipose ATF3 promotes adipose tissue lipolysis and the development of MASH.

ABSTRACT: The crosstalk between adipose tissue and the liver is finely controlled to maintain metabolic health. Yet, how adipose tissue controls toxic free fatty acid overflow into the liver remains incompletely understood. Here, we show that adipocyte activating transcription factor 3 (ATF3) was induced in human or mouse obesity. Adipocyte Atf3^-/- (Atf3^Adi-/-) mice developed obesity, glucose intolerance, and metabolic dysfunction-associated steatohepatitis (MASH) in chow diet, high-fat diet, or Western diet-fed mice. Blocking fatty acid flux by inhibiting hepatocyte CD36, but not the restoration of hepatic AMPK signaling, prevented the aggravation of MASH in Atf3^Adi-/- mice. Further studies show that the loss of adipocyte ATF3 increased lipolysis via inducing adipos

SUBMITTER: Hu S 

PROVIDER: S-EPMC11467330 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature