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primary cause of obesity is the energy imbalance
between calories consumed and expended while low-fat diet
and regular exercise are popular approaches to fight obesity
one easy alternative is simply to increase energy metabolism
it is known that the conversion of carbohydrates
or protein into fat uses ten times more calories
than simply storing fat in a fat cell so
we thought of a way to increase energy expenditure
by converting fat into glucose however
mammals cannot convert fatty acid into carbohydrate
because we lack glyoxylate enzymes, while
plants and bacteria can. so, we planned to introduce glyoxylate enzymes
into mammalian cells that will serve as an artificial futile cycle.
while the consequence of introducing nonnative cycle
unknown we found that UCLA research group
has recently build a constitutive glyoxylate shunt
into mammalian cell. they observed that
this increases fatty acid oxidation, unlike glyoxylate cycle
in plants and bacteria that allows the cell to conserve carbon
the group showed that mice expressing glyoxylate shunt
decreased plasma triglycerides likely a consequence
of increased fatty acid oxidation. however
the drawbacks of constitutive system are the risk of
fatty acid deficiency and inability to uptake greater amount of fatty acid in the
presence of high circulating fatty acid levels
then, we planned to elaborate UCLA group work
by introducing inducible system that allows
tunable fatty acid uptake by sensing fatty acid concentrations
we believe introducing inducible glyoxylate shunt into human liver cell
will serve as an artificial futile cycle. this will help obesity patients
increased energy expenditure and alleviate health complication
including cardiovascular diseases, cancers
and diabetes