Team:Hong Kong HKUST/projectdescription

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<div id="text" style="width:965px;"><br><br><center><font size = 5>Project description</font></center><br><br>
<div id="text" style="width:965px;"><br><br><center><font size = 5>Project description</font></center><br><br>
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The conversion of carbohydrates or protein into fat uses 10 times more calories of energy than simply storing fat in a fat cell*. This brought us attention to one method of burning calories - increase energy expenditure by converting fat into glucose. However, mammals cannot convert fatty acids into carbohydrate due to lack of glyoxylate enzymes, while plants and bacteria can. We planned to introduce glyoxylate enzymes into mammalian cells and introduce an artificial futile cycle.<br><br>
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While low-fat diet and regular exercise are popular approaches to fight obesity, one easy alternative is simply to increase energy metabolism. <br><br>
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While the consequence of introducing nonnative cycle unknown, James C. Liao’s group at UCLA recently has introduced glyoxylate shunt into mammalian liver cell to investigate fatty acid metabolism. They concluded that although fatty acids could not be converted into glucose in mammalian cells, human hepatocytes expressing the glyoxylate shunt have increased fatty acid oxidation and mice expressing the shunt were resistance to diet-induced obesity.<br><br>
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In terms of fat storage, conversion of carbohydrates or protein into fat uses ten times more calories of energy than simply storing fat in a fat cell. This brought us attention to one method of burning calories - increase energy expenditure by converting fat into glucose. However, mammals cannot convert fatty acids into carbohydrate due to lack of glyoxylate enzymes, while plants and bacteria can. We envision to introduce glyoxylate enzymes into mammalian cells and create an artificial futile cycle.<br><br>
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In addition to constitutive glyoxylate shunt introduced, HKUST 2013 team plans to elaborate Liao’s group work by introducing inducible system that allows tunable fatty acid uptake by sensing fatty acid concentrations. This inducible system prevents risk of fatty acid deficiency, where glyoxylate shunt no longer functions in a normal <br>range of fatty acid concentration. <br><br>
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While the consequence of introducing nonnative cycle unknown, Dean et al. at UCLA recently has introduced glyoxylate shunt into mammalian liver cell to investigate fatty acid metabolism (2009). They observed that although fatty acids could not be converted into glucose in normal mammalian cells, human hepatocytes expressing the glyoxylate shunt have increased fatty acid oxidation and mice expressing the shunt were resistance to diet-induced obesity.<br><br>
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HKUST team plans to investigate four different sensing mechanisms using: 1) fatty acid metabolism regulator protein (FadR), 2) peroxisome proliferator-activated <br>receptor-alpha (PPAR-alpha) 3) liver- fatty acid binding protein (FABP1) and 4) binding immunoglobulin protein, HSP5 or glucose regulated protein (GRP78). The four sensing mechanisms will be measured and compared. <br><br>
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In addition to introducing a constitutive glyoxylate shunt, our team plans to elaborate the UCLA study by introducing inducible system that allows tunable fatty acid uptake by sensing fatty acid concentrations. This inducible system prevents the risk of fatty acid deficiency, while greater fatty acid uptake at high circulating concentrations can be facilitated. Fatty acids uptake will be quantified to compare the activities in wild type cells and cells expressing constitutive and inducible glyoxylate shunt.<br><br>
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After construction of constitutive glyoxylate shunt, the most sensitive inducible circuit or promoter will be fused to regulate the glyoxylate shunt. The fatty acids will be quantified to compare uptake of fatty acids between wild type cells and cells expressing glyoxylate shunt. The uptake of fatty acids will be further compared between cells containing constitutive and inducible glyoxylate shunt. <br><br>
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We believe the introduction of an inducible glyoxylate shunt will serve as an artificial futile cycle in human liver cell that increases energy expenditure responding to high circulating fatty acid levels. This will help obesity patients increase expenditure of calories and alleviate health complications, including cardiovascular disease, diabetes, and cancers.
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<a href="http://science.howstuffworks.com/life/cellular-microscopic/fat-cell2.htm">*http://science.howstuffworks.com/life/cellular-microscopic/fat-cell2.htm</a>
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<br><br><br><br><center>© Copyright HKUST iGEM Team 2013, All Rights Reserved</center><br><br><br><br><br></div>
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<br><br><br><br><center>© Copyright HKUST iGEM Team 2013, All Rights Reserved</center><br><br><br><br><br><br><br></div>
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Latest revision as of 02:25, 9 August 2013



Project description


While low-fat diet and regular exercise are popular approaches to fight obesity, one easy alternative is simply to increase energy metabolism.

In terms of fat storage, conversion of carbohydrates or protein into fat uses ten times more calories of energy than simply storing fat in a fat cell. This brought us attention to one method of burning calories - increase energy expenditure by converting fat into glucose. However, mammals cannot convert fatty acids into carbohydrate due to lack of glyoxylate enzymes, while plants and bacteria can. We envision to introduce glyoxylate enzymes into mammalian cells and create an artificial futile cycle.

While the consequence of introducing nonnative cycle unknown, Dean et al. at UCLA recently has introduced glyoxylate shunt into mammalian liver cell to investigate fatty acid metabolism (2009). They observed that although fatty acids could not be converted into glucose in normal mammalian cells, human hepatocytes expressing the glyoxylate shunt have increased fatty acid oxidation and mice expressing the shunt were resistance to diet-induced obesity.

In addition to introducing a constitutive glyoxylate shunt, our team plans to elaborate the UCLA study by introducing inducible system that allows tunable fatty acid uptake by sensing fatty acid concentrations. This inducible system prevents the risk of fatty acid deficiency, while greater fatty acid uptake at high circulating concentrations can be facilitated. Fatty acids uptake will be quantified to compare the activities in wild type cells and cells expressing constitutive and inducible glyoxylate shunt.

We believe the introduction of an inducible glyoxylate shunt will serve as an artificial futile cycle in human liver cell that increases energy expenditure responding to high circulating fatty acid levels. This will help obesity patients increase expenditure of calories and alleviate health complications, including cardiovascular disease, diabetes, and cancers.



© Copyright HKUST iGEM Team 2013, All Rights Reserved