Adipocyte-specific Mlkl knockout mitigates obesity-induced metabolic dysfunction by enhancing mitochondrial functions.

ABSTRACT: Obesity is a global epidemic characterized by chronic low-grade inflammation and metabolic dysfunction, with adipose tissue playing a pivotal role in these processes. The mixed lineage kinase domain-like pseudokinase (MLKL) is a critical mediator of necroptosis but also exhibits noncanonical roles in metabolic regulation. This study aimed to investigate the adipocyte-specific functions of MLKL in obesity. Using adipocyte-specific Mlkl knockout (Mlkl^Adi-KO) mice, we observed reduced susceptibility to high-fat diet (HFD)-induced obesity, enhanced glucose tolerance, and improved insulin sensitivity. Mlkl^Adi-KO mice showed elevated energy expenditure independent of changes in food intake or locomotor activity, correlating with increased mitochondrial function and reduced

SUBMITTER: Tokgozoglu J 

PROVIDER: S-EPMC12501060 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature