How much we want to eat, in other words our appetite, and how much energy we burn, are both controlled by a hormone known as leptin. Leptin is made by fat tissue and it passes through the circulation to the brain, where it modifies the activity of several types of nerve cell, including POMC nerves, to signal to the body that it does not need to eat more and that it needs to burn more energy.
As obesity can be caused if leptin-mediated signaling goes awry, much effort is being expended trying to identify the signaling pathways activated by leptin. Joel Elmquist and colleagues, at the University of Texas Southwestern Medical Center, Dallas, have provided new insight into the signaling pathways by which leptin mediates its effects on POMC nerves in mice.
In the study, analysis of the brain tissue of normal mice indicated that leptin caused rapid activation of POMC nerves. These effects of leptin could be blocked by inhibitors of a signaling molecule known as PI3K and mice with genetically disrupted PI3K signaling in POMC cells failed to activate the nerve cells in response to leptin.
Furthermore, targeted disruption of PI3K interfered with leptin-induced suppression of feeding. Despite these short-term consequences, the absence of POMC PI3K signaling had no detectable impact on long-term regulation of body weight, leading the authors to propose that POMC PI3K signaling is essential for suppressing appetite, but that PI3K signaling in POMC neurons is not the primary signaling pathway by which leptin regulates long-term energy expenditure.
Journal reference: Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. Journal of Clinical Investigation. April 1, 2008.
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