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Full Abstracts – PHYSIOLOGY AND AGING
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Role of oenocytes in metabolic response to starvation.
Debamita Chatterjee, Heinrich Jasper. Department of Biology, University of Rochester, Rochester,
NY.
Organisms need to maintain metabolic homeostasis in order to live a healthy lifespan. In mammals, the liver plays a critical role in metabolic homeostasis
under different environmental perturbations. Surprisingly, there is very little evidence of a corresponding tissue in Drosophila. Gutierrez and coworkers
(2007) demonstrated a novel hepatocyte-like role for a previously mysterious class of specialized cells in Drosophila larva called oenocytes. The oenocytes
are arranged in ribbon-like clusters along the inner cuticle of each abdominal segment. They specifically showed that oenocytes regulate the uptake of lipids
during starvation much like the mammalian hepatocytes. In addition, they also express a specific set of genes homologous to mammalian liver. We wanted to
characterize oenocytes in adult flies especially with respect to their role in regulating metabolic homeostasis under starvation conditions.We performed a
transcriptome analysis of the genes expressed in oenocytes under starvation. We observed an upregulation of several key metabolic genes like neoglucogenic
enzyme pepck, triacylglycerol lipases and adipokinetic hormone receptors GRHRI and II. In order to test the oenocyte-specific expression of several
transgenes, we cloned a oenocyte-specific mifepristone-inducible driver. Using this driver, it was found that there is increased starvation sensitivity of flies
in which oenocytes were ablated and of flies in which there was a oenocyte-specific blocking of Insulin signaling pathway (IIS) pathway. In addition, we
observed a loss of upregulation of pepck and GRHR1 transcript levels under starvation conditions when IIS pathway was blocked in the oenocytes as
compared to the wild type flies. Preliminary studies of the metabolic profile indicated that there was less glycogen and trehalose in the oenocyte-ablated flies
compared to wild-type. All these results suggest a oenocyte-dependent regulation of metabolic homeostasis through the novel interaction of IIS and
adipokinetic-hormone pathways. Future experiments are directed to corroborate the aforementioned hypothesis.
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Juvenile hormone regulation of lipid metabolism through insulin signaling.
Hua Bai, Ping Kang, Marc Tatar. Ecology & Evolutionary Biol, Brown
University, Providence, RI.
Juvenile hormones (JH) produced in corpora allata (CA) are involved in a variety of biological processes. Beside the role on female vitellogenesis, the
effects of JH and its analog on lipid metabolism have also been studied in several insects. However, the underlying mechanism is poorly understood. Here
we investigated the regulation of JH on lipid metabolism in female Drosophila. We found that short period application of JH analog (methoprene) increases
the level of triglyceride (TAG), while CA ablated (CAKO) flies and putative JH receptor (Met) mutants have reduced TAG. Interestingly, we identified an
insulin-like peptide (dilp6) whose expression can be directly induced by methoprene application in fat body culture in vitro. This induction requires Met and
Kr-h1, two key players involved in JH signaling network. Overexpression of either Kr-h1 or dilp6 using a fat body driver promotes the accumulation of TAG
in fat body. Furthermore, the expression of Kr-h1 and dilp6 are altered in responding to different nutrient conditions. These results suggest that JH may
regulate lipid metabolism through a fat body expressed insulin-like peptide.
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An Interleukin-6 like cytokine regulates systemic insulin signaling by conveying the 'fed' state from the fat body to the brain.
Akhila Rajan
1
, Norbert
Perrimon
1,2
. 1) Department of Genetics, Harvard Medical School, Boston, MA; 2) Howard Hughes Medical Institute, 77 Ave Louis Pasteur, Boston, MA.
Organisms constantly adapt their energy needs in accordance to their nutritional status. This process, referred to as 'energy homeostasis', involves the
regulation of sugar and lipid stores depending on nutritional availability. Genetic studies of physiological responses in
Drosophila
have revealed that many
parallels exist between invertebrate and mammalian homeostasis. In particular, many of the organs that control nutrient uptake, storage and catabolism in
vertebrates, have analogs in the fly.
The fat body (FB) in the fly functions as the 'nutrient sensor' and sends remote signals to the islet-like cells in the brain to release insulin and regulate
energy balance. Though the TOR pathway has been shown to play a crucial role in nutrient sensing in the FB, the identity of the humoral signal(s) involved
in communication between the FB and the brain is unknown.
We have identified a
Drosophila
Interleukin (IL)-6 like gene, which, when perturbed specifically in the FB, results in a systemic reduction in cell size. In
addition, these flies have reduced triacylglycerol levels and increased circulating sugars indicative of metabolic defects. They feed normally but accumulate
lipids in the oenocytes even under 'fed' conditions, implying that they physiologically phenocopy starvation. Altering the levels of this gene in the FB affects
insulin accumulation in the brain. However, a knock-down of this gene in other tissues such as the muscle has no effect on systemic growth and metabolism.
Additional data suggest that this IL-6 family member conveys the ‘fed’ state in flies and affects systemic growth and metabolism by remotely controlling
insulin secretion in the brain.
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MASOP coordinates imaginal disc growth and maturation with developmental timing.
Julien Colombani, Ditte Andersen, Pierre Leopold. Institute of
Developmental Biology and Cancer, Nice, France.
Little is understood about how developmental timing is coordinated with maturation/patterning of an animal during development. Earlier wing disc
transplantation/regeneration experiments have demonstrated an important role for imaginal tissues in this coupling. Wounding of discs delays pupal molt
allowing the wounded tissue to regenerate before entering metamorphosis. The nature of the molecular signal released from the discs to control
developmental timing has yet to be identified. We have carried out an RNAi-based genome wide screen to identify molecules produced in the disc that are
responsible for the developmental delay observed in animals with either neoplastic or minute-like imaginal discs. We screened 10.100 RNAi lines of the
VDRC phiC31 collection and isolated 121 transgenic lines able to rescue developmental delay induced in the neoplastic growth conditions. Among them, we
identified MASter Of Pupae (MASOP), a gene whose silencing rescued the delay in both of our testerlines. MASOP encodes a putative secreted peptide and
is regulated at the transcription level as we found MASOP levels highly up regulated in a microarray experiment for developmentally delayed neoplastic
discs. Overexpression of MASOP in imaginal tissues with a 2-day development delay without any visible effect on disc shape or patterning. We propose that
MASOP is an inhibitory signal produced and potentially secreted from injured/slow growing mitotic tissues to delay pupariation, permitting
regeneration/completion of growth to occur.