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Brain’s Appetite Center Uses Fat For Fuel

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Researchers at Yale School of Medicine have found the brain’s appetite center uses fat for fuel by involving oxygen free radicals—molecules associated with aging and neurodegeneration. The findings, reported in the journal Nature, suggest that antioxidants could play a role in weight control.

The study’s lead authors were Sabrina Diano and Tamas Horvath, who are an associate professor and professor, respectively, in the Departments of Obstetrics, Gynecology & Reproductive Sciences and Neurobiology. Horvath is also chair of the Section of Comparative Medicine.

“In contrast to the accepted view, the brain does use fat as fuel,” said Horvath. “Our study shows that the minute-by-minute control of appetite is regulated by free radicals, implying that if you interfere with free radicals, you may affect eating and satiety.”

The results also imply, added Horvath, “that each time a feeling of fullness or satiety is reached during a meal, you may be chipping away some time from your maximum lifespan as the most free radicals are produced when satiety-promoting brain cells are active.”

Diano, Horvath and colleagues conducted the study in mice to better understand how the brain mediates neuronal activation in response to ghrelin, a hormone produced in the stomach and previously associated with growth hormone release, appetite, learning and memory.

They found that ghrelin-induced increase in appetite is driven by burning fat in hypothalamic mitochondria, which produces free radicals that are scavenged by a mitochondrial protein called uncoupling protein 2 (UCP2)

“The timing of taking antioxidants may be critical for the control of appetite,” said Diano. “If taken on an empty stomach antioxidants may further increase appetite, however when taken with food, they may affect satiety. Further studies are needed to determine whether any regiment of orally taken antioxidants could be used to control appetite in animals and humans.”

Nature advance online publication 30 July 2008 | doi:10.1038/nature07181
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Zane B. Andrews, Zhong-Wu Liu, Nicholas Walllingford, Derek M. Erion, Erzsebet Borok, Jeffery M. Friedman, Matthias H. Tschöp, Marya Shanabrough, Gary Cline, Gerald I. Shulman, Anna Coppola, Xiao-Bing Gao, Tamas L. Horvath & Sabrina Diano

The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.

Written by huehueteotl

July 31, 2008 at 7:38 am

Posted in Neuroscience

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  1. […] The key thing to realize about your appetite & drive to eat and/or binge is that they are controlled by “lizard” brain; willpower really has nuttin’ to do wid nuttin’. Meaning: if you’re trying to lose weight or feel like you’re starving all the time, it’s not your imagination!  It means you need to do two things: eat more protein at meals (protein + fat = maximum satiety) and give your body the nutrients it’s looking for so it stops tormenting you with weird food cravings & inducing you to binge-eat.  You also don’t want your blood sugar fluctuating; when it drops, it tells your brain: “I want-need-must-have food…NOW!” (image: source) […]


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