Mathew Sebastian
Biology 303 Term Paper
Schlank: a gene that can control growth and body fat in Drosophila
There is a homeostasis of energy within all animals that is under control of evolutionary
conserved nutrient-sensing systems. Because of the importance of homeostasis, there are several
families of secreted peptide hormones that regulate and fine-balance carbohydrate and lipid
metabolism to match specific energy requirements. When an organism is growing, there is an
even more specific coordinated regulation of the lipid metabolism that is important on both the
cellular and organismal level.
Looking at the cellular level of an organism, there are sterols in mammals that control the
release of sterol-regulatory element-binding protein (SREBP) from cell membranes. They do this
by having a negative feedback control system on the synthesis of fatty acids (FAs) and
phospholipids (Dobrosotskaya et al., 2002; Seegmiller et al., 2002; Kunte et al., 2006). The
SREBPs are transcription factors that check over the composition of the cell membrane and
change lipid synthesis to match the specific energy requirements of an organism at a particular
time.
When looking at the organismal level, the only way to control the homeostasis of energy
in the body is to have the ability to control the balance between lipid synthesis, storage and lipid
mobilization during varying conditions from energy abundance to energy deprivation (Hay and
Sonenberg, 2004; Zechner et al., 2005). In Drosophila, the stored fats are triacylglycerols
(TAGs), which builds up in their bodies (Martin and Parton 2006). Lipolysis, the breakdown of
stored fats, of the triacylglycerols is made possible by enzymes called lipases which release free
FAs or sn-1,2-diacylglycerol (DAGs) in mammals and insects. If there is anything wrong with
the regulation of the balance between lipolysis and lipogenesis it may lead to metabolic
abnormalities such as lipodystrophy syndromes, insulin resistance in humans or obesity. Obesity
is the medical condition where excess body fat has accumulated to the extent that it may have
adverse effects on health. Over 400 million adults are obese, with the rate of obesity in the
United States, Australia, and Canada increasing faster than the overall world rate of obesity.
Bauer et al. (2009) have investigated and identified a new gene that shows signs of regulating
growth and lipid homeostasis in Drosophila. They named the gene schlank which means slim in
German.
Normally, after hatching, Drosophila go through three larval instar stages before they
form their pupa, which occurs around 96–120 h after hatching. During this development, the
wildtype pupae increase their body size by about 200-fold. In this investigation of the schlank
gene, two hemizygous schlank mutants were made: one was termed schlankG0349 the other
being schlankG0061. These alleles were isolated by screening the Gottingen X-chromosome
collection of P-lines (Peter et al., 2002). These hemizygous schlank mutants did not grow as fast
as the wildtype and also had pronounced growth defects which were dependent on the strength of
the allele (Figure 1A–C). Schlank mutants that carried the stronger schlankG0349 gene, the case
where schlank was more underexpressed, died three days into the experiment, and thus they were
not able to grow to the larval stage (Figure 1A–B). In contrast, when the mutants carried the
weaker schlankG0061 allele, the case where the gene was underexpressed but not as much as in
schlankG0349, they were able to reach the third instar larval stage although they still developed
more slowly compared to the wildtype. Quantitative real-time PCR experiments showed that the
levels of schlank transcripts were reduced to less than 40% in hemizygous schlankG0061 larvae
and to less than 10% in hemizygous schlankG0349 larvae when compared to the wildtype
(Figure 1C). Next, when an antibody was made against a schlank-specific oligopeptide and was
used to identify the C-terminus of the schlank protein, they found that the level of schlank
protein was reduced by about 20% in the schlankG0061 and by 40% in the schlankG0349
mutants (Figure 1D). Though these percentages differ from the expected amount given from the
quantitative real-time PCR, they still correlate well with the numbers received from it.
(Figure 1A shows the larval growth of the schlank mutants versus the wildtype, the
control. The schlank mutants are visibly much smaller than the wildtype. Figure 1B shows the
average length of the control versus the schlank mutants).
(Figure 1C shows the reduced schlank RNA expressions in schlank mutants as compared
to the wild type. Figure 1D is the determination of residual schlank protein in the mutants- it was
reduced to 80% in schlankG0061 and 60% in schlankG0349 compared to the wildtype)
(Figure 2A shows that the TAG and FA levels were reduced to a different extent that still
correlates well with the expression of schlank. The FAs and TAGs were separated using TLC
with n-hexene/diethylether/glacial acetic acid (70:30:1.) Table 1 shows the reduced levels as
well. These numbers are all relative to the wild type).
Bauer et al. (2009) identified schlank as an important regulator of the balance between
lipogenesis and lypolysis and found that schlank mutant larvae that had schlank downregulated
by RNAi were largely devoid of storage fats, the TAGs. Usually lipids and carbohydrate
metabolism is regulated by hormones, but it is not certain how the schlank gene is regulated in
the body.
What is interesting though is that when experiments were run to test what would happen if
the schlank gene was overexpressed, it restored the fat body development and led to increasing
amounts of TAGs, FAs, and DAGs in the body. Also, mammals carry a group of genes that are
very similar to the schlank gene. Conducting research on these similar genes may lead scientists
to finding new methods and treatments to fighting obesity.
Works Cited:
Bauer R, Voelzmann A, Breiden B, Schepers U, Farwanah H, Hahn I, Eckardt F, Sandhoff K,
Hoch M (2009) Schlank, a member of the ceramide synthase family controls growth and
body fat in Drosophila. The EMBO Journal: 1-11.
Collins, Anne. "Obesity Statistics." Http://www.annecollins.com. 4 Oct. 2007. Web. 5 Nov.
2009. <http://www.annecollins.com/obesity/statistics-obesity.htm>.
Dobrosotskaya IY, Seegmiller AC, Brown MS, Goldstein JL, Rawson RB (2002) Regulation of
SREBP processing and membrane lipid production by phospholipids in Drosophila.
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Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18: 1926–1945
Kunte AS, Matthews KA, Rawson RB (2006) Fatty acid Auxotrophy in Drosophila larvae
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Martin S, Parton RG (2006) Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol
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Peter A, Scho¨ ttler P, Werner M, Beinart N, Dowe G, Burkert P, Mourkioti F, Dentzer L, He Y,
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on the X chromosome of Drosophila. EMBO Rep 3: 34–38.
Seegmiller AC, Dobrosotskaya I, Goldstein JL, Ho YK, Brown MS, Rawson RB (2002) The
SREBP pathway in Drosophila: Regulation by Palmitate, not Sterols. Dev Cell 269: 229–
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Zechner R, Strauss JG, Haemmerle G, Lass A, Zimmermann R (2005) Lipolysis: pathway under
construction. Curr Opin Lipidol 16: 333–340.