Nutrient Signaling and Developmental Timing of Maturation - Current Topics in Developmental Biology - page 46

fed on a high fat diet become obese in an insulin/TOR dependent manner
with an increase in free glucose accompanied with a drop in DILP2 transcript
levels ( Birse et al., 2010 ). Unlike fatty acids, cholesterol is a neutral lipid that
serves as a substrate for steroid synthesis ( Huang, Suyama, Buchanan, Zhu, &
Scott, 2005; Huang, Warren, & Gilbert, 2008 ). Since insects are sterol auxo-
trophs, they require a dietary source of cholesterol or other sterols that can be
converted into ecdysteroids for their development. Although many steps in
the uptake and trafficking of cholesterol remain unclear, it has been demon-
strated that the niemann-pick type C ( npc ) genes are essential for delivery of
cholesterol for ecdysone synthesis ( Huang et al., 2005; Huang, Warren,
Buchanan, Gilbert, & Scott, 2007 ). These genes are believed to be important
for intestinal absorption of cholesterol and are required specifically in the PG
to deliver cholesterol for the first step in the ecdysone biosynthetic pathway,
the conversion of cholesterol to 7-dehydrocholesterol (7dC). Larvae lacking
npc1a arrest development in L1, a phenotype that can be at least partially res-
cued by providing high levels of cholesterol in the diet ( Huang et al., 2005 ).
Interestingly, a recent study suggests that dietary sterols from hempseed and
cholesterol may increase growth and accelerate pupariation in Drosophila
( Lee et al., 2010 ). While cholesterol is a precursor of ecdysone, which might
explain the acceleration of developmental progression, it is less clear how ele-
vated cholesterol levels increases growth, although cholesterol has essential
roles in cell membranes.
Although poor nutrition delays development, nutrition past an upper
threshold limited by the maximal growth rate cannot further accelerate
pupariation. Beyond this point only genetic perturbations that result in prema-
ture release of ecdysone are known to accelerate pupariation ( Ou, Chwalla,
Landgraf, & van Meyel, 2008; Rewitz et al., 2009 ). However, addition of
royalactin to the diet was recently found to accelerate development
( Kamakura, 2011; Yamanaka &O'Connor, 2011 ). Royalactin is a protein iso-
lated from the food source compoundRoyal Jelly, that bees feed their larvae to
promote them to become queens instead of workers. This changes the epige-
netic program of the larvae ( Kucharski, Maleszka, Foret, & Maleszka, 2008;
Maleszka, 2008 ) and accelerates growth, giving rise to animals with a larger
body size and 10 times the lifespan of the workers. Surprisingly, Drosophila feed
with royalactin show a similar phenotype of increased body size, extended
lifespan and shortened developmental time ( Kamakura, 2011; Kayashima,
Yamanashi, Sato, Kumazawa, & Yamakawa-Kobayashi, 2012 ). The effect
of royalactin is not nutritional, as increasing protein levels in food do not have
a similar effect. Instead, dietary royalactin activates either directly or indirectly