Pck1 Deficiency Drives Mitochondrial Dysfunction and Cellular Senescence in Adipocytes

Pck1 expression was downregulated in both gonadal and inguinal white adipose tissues during aging.

• Cellular senescence in white adipose tissues is linked to aging, but mechanisms are not fully clear.
• Adipocyte-specific deficiency of Pck1 accelerated signs of inflammation and metabolic issues.
• Loss of Pck1 led to impaired export of important metabolic intermediates, resulting in fumarate accumulation in adipocytes.
• Supplementing with fumarate disrupted the normal function of mitochondria in adipocytes and increased oxidative stress.
• This oxidative stress triggered the release of mitochondrial DNA, which may activate inflammatory pathways associated with obesity.
• Overexpression of fumarate hydratase significantly lowered fumarate levels and reduced inflammation in adipocytes.

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