During this reporting period the Laboratory of Genetics and Physiology has made progress in the understanding of mechanisms used by cytokines to control the physiology of liver and the hypothalamus.? ? Liver? Previously we had established that cytokine signaling (possibly growth hormone) through the transcription factor STAT5 is essential to protect the liver from hepatosteatosis (fatty liver) and its ability to regenerate. We have now performed and published additional studies on underlying molecular mechanisms. In particular, we have identified signaling cascades downstream of STAT5 that control the growth hormone - mediated physiology of hepatocytes.? ? Energy balance and metabolism? It had been known that cytokines can control energy balance by targeting certain cell populations in the CNS. For example, it is well established that leptin controls the energy balance through the transcription factor STAT3. It had also been known that another cytokine, GM-CSF, can control feeding behavior but its molecular underpinnings were elusive. GM-CSF, like many other cytokines, can activate STAT5 and we addressed the relevance of this observation. LGP scientists deleted the STAT5 genes from the mouse CNS and observed that these mice displayed an altered energy balance and developed obesity. Molecular and physiological studies in neurons of these mice linked GM-CSF signaling through STAT5 to food intake, thermoregulation and maintenance of body weight. These studies contribute to the general understanding on how cytokines control neurons and thus our apetite.
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