A liver-fat crosstalk for iron flux during adipose browning.

In adipose FoxO1 KO (adO1KO) mice, active crosstalk between the liver and adipose tissue supplies iron required for augmented mitochondrial biogenesis during beiging of adipocytes. Increased mitochondrial biogenesis plus sustained mitophagy upregulates mitochondrial content and respiratory capacity, improving systemic metabolism. In adipsoe Atg7 KO (ad7KO) mice, however, a higher mitochondrial content results from impairment in mitophagy and accumulation of poor-quality-controlled mitochondria, thereby reducing mitochondrial capacity. As mitochondrial biogenesis is unchanged, the liver-fat crosstalk is silenced. ↔, unchanged; ↑, upregulated; ↓, downregulated. The gray dashed line indicates the absence of activation of a liver-fat crosstalk for iron supply.