Attaining and maintaining a healthy body weight is achieved by the regulation of energy homeostasis. Energy homeostasis, the ability of an organism or cell to maintain normal biological states during adjustments to environmental changes, is governed by complex neuronal circuitry and numerous signaling molecules. When control mechanisms for energy homeostasis go wrong, the result is weight loss or obesity. In a paper published in the open access journal PLoS Biology, Allison Wanting Xu et al. reveal that progressive degeneration of two types of hypothalamic neurons affects energy balance associated with aging.
Located in the hypothalamus, the two types of neurons that regulate fat buildup, or adiposity, contain proopiomelanocortin (Pomc) and agouti-related protein (Agrp) , two neuropeptides which appear to affect food intake in opposite ways when administered to animals. To investigate more fully the roles that Pomc and Agrp neurons play in energy homeostasis, Allison Wanting Xu et al. have constructed mouse strains in which the Pomc or Agrp neurons are lost progressively after birth. They selectively deleted the gene for the mitochondrial transcription factor A (Tfam) in Pomc- or Agrp-expressing neuronal cells. By six months old, the researchers report, the engineered mice had lost many of their Pomc or Agrp neurons but no other neurons.
Like aging humans, mice in which Pomc neurons had died became progressively fatter because of an increased food intake and reduced energy expenditure. Mice that had lost Agrp neurons weighed slightly less than control animals. Mice engineered so that both types of neurons died weighed more than control mice but less than those lacking just Pomc neurons. These results indicate that the regulation of adiposity by Pomc and Agrp neurons is not simply a matter of releasing these two neuropeptides.
Xu et al. made an additional, unexpected observation. After food deprivation, mice normally increase
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Contact: Paul Ocampo
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Public Library of Science
28-Nov-2005