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Poster Full Abstracts - Physiology and Aging
Poster board number is above title. The first author is the presenter
326
727A
The
Drosophila PGC1
-α Homolog
spargel
Modulates the Physiological Effects of Endurance Exercise.
Lindsey Healy, Martin Tinkerhess, Matthew
Morgan, Erin Matthys, Li Zheng, Robert Wessells. Univ Michigan, Ann Arbor, MI.
Endurance exercise is a promising, inexpensive intervention that is thought to provide substantial protection against several age-related pathologies, as well
as inducing acute changes to endurance capacity and metabolism. Recently, it has been established that endurance exercise induces conserved alterations in
physiological capacity in the invertebrate
Drosophila
model. If the genetic factors underlying these exercise-induced physiological alterations are widely
conserved, then invertebrate genetic model systems will become a valuable tool for testing of genetic and pharmacological mimetics for endurance training.
Here, we assess whether the
Drosophila
homolog of the vertebrate exercise response gene
PGC1
-α,
spargel (srl)
, is necessary or sufficient to induce
exercise-dependent phenotypes. We find that reduction of
srl
expression levels acutely compromises mobility and fatigue resistance, as well as exercise-
induced improvement in both assays. Conversely, muscle/heart specific
srl
overexpression improves mobility and cardiac performance in unexercised flies.
In addition, we find that
srl
overexpression acts additively to facilitate the impact of endurance exercise on mobility, fatigue resistance and cardiac
performance, indicating that other factors also act in parallel to
srl
to regulate exercise-induced physiological changes in muscle and heart.
728B
Effects of dietary fatty acids and temperature on mitochondrial function.
Marissa A. Holmbeck
1
, David M. Rand
2
. 1) Molecular Biology, Cell Biology,
and Biochemistry Dept., Brown University, Providence, RI; 2) Ecology and Evolutionary Biology Dept., Brown University, Providence, RI.
Energy metabolism is modulated by both temperature and diet. These environmental variables can alter cellular functions as well as the fatty acid
composition of membranes. According to the fluid mosaic model of membrane structure, phospholipids are arranged in a fluid bilayer with integral proteins
free to move within this structure. The degree of membrane saturation and temperature may interact to modulate the fluidity of the membrane and activity of
membrane-associated enzymes. This is particularly important in mitochondria where the integrity of the double membrane structure of the organelle is
critical to the production of cellular energy. To dissect the interaction between temperature and fatty acid diets on mitochondrial function, flies were raised
on media containing specific saturated, monounsaturated, or polyunsaturated fatty acids supplements at low concentrations. Flies were maintained on control
and fatty acid diets for ten days at two different temperatures. To assay mitochondrial function under these conditions mitochondrial respiration, reactive
oxygen species production, and membrane potential were measured. A large thermal effect on respiration was observed, while only subtle effects of diet
were seen on activity of electron transport chain complexes. Additionally, longevity was measured to dissect the interactions of fatty acid and temperature
manipulations on lifespan, and the results are not consistent with the simple mitochondrial free radical theory of aging. We hypothesize that the varied
effects of temperature and fatty acid supplementation are modulated by acclimation of membrane composition in order to maintain membrane fluidity,
regardless of diet.
729C
Catalytically Inactive Triosephosphate Isomerase Rescues TPI Deficiency.
Bartholomew P Roland
1,2,3
, Kimberly Stuchul
1
, Michael J Palladino
1,3
. 1)
Pittsburgh Institute for Neurodegenerative Diseases, Pittsburgh, PA; 2) University of Pittsburgh Graduate Program in Molecular Pharmacology, Pittsburgh,
PA; 3) University of Pittsburgh Department of Pharmacology & Chemical Biology, Pittsburgh, PA.
Triosephosphate isomerase (TPI) is a glycolytic enzyme that converts dihydroxyacetone phosphate (DHAP) into glyceraldehyde-3-phosphate (G3P).
Dysfunction in TPI will lead to a number of diseases collectively known as TPI deficiency glycolytic enzymopathies. We have isolated a point mutation in
the Drosophila TPI gene called sugarkill that causes symptoms similar to those in human patients, including seizures, paralysis, premature death, and
neurodegeneration. We have established that this mutation increases the degradation of TPI, and animal phenotypes can be attenuated by inhibiting the
proteasome or overexpressing the mutant TPI. Here we show that TPI sugarkill behavioral phenotypes can be rescued through the addition of a catalytically
inactive TPI enzyme.
730A
The regulation of fat storage by
Mio
in
Drosophila
.
Eric D. Sassu, Jacqueline E. McDermott, Brendan J. Keys, Justin R. DiAngelo. Department of
Biology, Hofstra University, Hempstead, NY.
During nutrient excess, triglycerides are synthesized and stored to provide energy during times of famine. One of the major pathways controlling fat
synthesis during nutrient excess leads to the activation of carbohydrate response element binding protein (ChREBP), a transcription factor that induces the
expression of a number of glycolytic and lipogenic enzymes. However, the molecular mechanisms regulating ChREBP activation and function are not fully
understood. In this study, we characterized the role of the
Drosophila
homolog of ChREBP,
Mlx interactor (Mio)
, in controlling fat accumulation in larvae
and adult flies. Lowering
Mio
levels using RNAi specifically in the larval or adult fat body leads to a lean phenotype. This phenotype results from decreasing
the amount of fat stored per cell while the total number of fat body cells produced remains unchanged. A lean phenotype is also observed when the gene
bigmax
, the fly homolog of the ChREBP binding partner Mlx, is decreased in the fat body suggesting that Mio and bigmax may be acting together to
promote triglyceride storage. Interestingly, depleting
Mio
in the fat body results in decreased feeding providing a potential cause of the lower triglycerides
observed in these animals. Together these data indicate a role for
Mio
in controlling fat accumulation in
Drosophila
and suggests that it may act as a nutrient
sensor in the fat body to coordinate feeding behavior with nutrient availability.
731B
Transgenerational Inheritance of Metabolic State in
Drosophila
.
Rebecca A Somer, Matt Sieber, Carl Thummel. University of Utah, Salt Lake City, UT.
Poor nutrition has been implicated as a key causal factor in the development of metabolic syndrome. Recent data, however, has suggested that parental diet
can also have a dramatic impact on the metabolic state of our children. Several human studies have shown that nutrient deprivation, gestational diabetes, and
obesity have an effect on the metabolic state of children at both adolescence and adulthood. In addition, studies in rodents have shown that the adult progeny
of mothers subjected to nutrient depletion display hallmarks of obesity and diabetes. Similar results are seen in the progeny of male mice fed a low protein
diet, along with changes in the expression of genes involved in lipid metabolism (Carone et al 2010
Cell
). These results suggest that the inheritance of a
metabolic program is more than a gestational effect, as it can be inherited from either parent before conception. All of these studies, however, are correlative,