In mice, turning on the YAP/TAZ proteins in fat cells causes those cells to lose their fat content and revert to a less mature state, while also raising leptin levels in the blood without changing...
Mechanism
Synthesis from 1 study
When YAP and TAZ are turned on in fat cells, they make the cells lose their fat and become stem-cell-like, while also forcing the body to produce lots of leptin even when there’s almost no fat left (10.1038/s42255-024-01045-4). This high leptin tells the liver to burn fat for energy instead of...
Most probable mechanism
When YAP and TAZ proteins are activated in fat cells, they turn off the genes that keep fat cells full of oil, causing them to shrink and become more like stem cells. At the same time, these same proteins directly turn on the gene that makes the hormone leptin, so even when there's almost no fat left, leptin levels stay high. This high leptin tells the body to burn more fat for energy, especially in the liver, which prevents dangerous fat buildup in the liver and keeps blood sugar stable — all without needing fat tissue.
Deletion of LATS1 and LATS2 in adipocytes prevents phosphorylation of YAP and TAZ, allowing their nuclear translocation where they bind TEAD transcription factors to repress PPARG-driven adipogenic gene expression, leading to loss of lipid droplets and delipidation of mature adipocytes (10.1038/s42255-024-01045-4).
Nuclear YAP/TAZ-TEAD complexes directly bind to a conserved enhancer located 28 kb upstream of the leptin gene transcription start site, activating Lep transcription independently of adipose tissue mass (10.1038/s42255-024-01045-4).
Elevated leptin secretion increases whole-body energy expenditure and shifts substrate utilization toward fatty acid oxidation, as evidenced by reduced respiratory exchange ratio and increased oxygen consumption (10.1038/s42255-024-01045-4).
Increased fatty acid oxidation occurs preferentially in the liver, driven by upregulation of Ppargc1a (Pgc1a), which enhances mitochondrial fatty acid catabolism and prevents ectopic lipid accumulation (10.1038/s42255-024-01045-4).
Delipidated adipocytes acquire progenitor-like characteristics, expressing markers such as Dlk1, Ly6a, and Pdgfra, and retain the capacity to re-enter the adipogenic lineage under permissive conditions (10.1038/s42255-024-01045-4).
Evidence from Studies
Supporting (1)
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Hippo–YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass
Contradicting (0)
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