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(
Bi et al., 2012
). On the other hand,
Dm
PLIN2 mutants had smaller LDs, apparently
due to lack of
Dm
PLIN2 function in protecting LDs from
brummer
-mediated lipol-
ysis (
Bi et al., 2012; Gronke et al., 2007
). Lipid storage function in the
Dm
PLIN1 and
Dm
PLIN2 double mutant is further impaired, exhibited by even smaller LDs in these
double-mutant flies. However, it is important to note that the double-mutant flies still
formed LDs, suggesting that there are additional PLIN 1/2-independent mechanisms
for storing lipids in the form of LDs.
4.3.2
Lipases
Hormone-sensitive lipase (HSL) was the first lipase known to hydrolyze triacylgly-
cerides in rat adipose tissue (
Holm et al., 1988
) until the identification of ATGL
(
Jenkins et al., 2004; Villena, Roy, Sarkadi-Nagy, Kim, & Sul, 2004;
Zimmermann et al., 2004
). While HSL could catalyze the hydrolysis of triacylgly-
cerides and diacylglycerides as well as various cholesterol ester species (
Holst et al.,
1996
), ATGL showed high substrate specificity for triacylglycerides (
Zimmermann
et al., 2004
).
d
HSL
is a homolog of human HSL, interacts closely with
Dm
PLIN1, and is the
key lipase to breakdown LDs (
Bi et al., 2012
). Although the details need to be elu-
cidated, the signaling from the AKH receptor (AKHR) results in
Dm
PLIN1 and
d
HSL phosphorylation in a similar manner as mammalian
b
-adrenergic signaling
(
Beller et al., 2010; Bi et al., 2012; Kuhnlein, 2011
). The role of
d
HSL in acute
lipolysis was demonstrated by starvation challenge.
d
HSL mutant third instar larvae
had significantly larger LDs under starved conditions, an indication of a profound
lipolysis defect.
Similar to the lack of an obese phenotype in HSL knockout mice, the
d
HSL
mutant is only slightly fatter than wild-type flies under normal feeding conditions.
Conversely, a loss-of-function mutation in the brummer gene (
bmm
, ortholog of
the mammalian ATGL) results in obesity in adult flies, and maternal
bmm
mutants
died during the embryonic stage, pinpointing its role in mediating lipolysis under
basal situations. The
bmm
and AKHR double-mutant fly presents an extremely obese
phenotype (
Gronke et al., 2007
), suggesting
bmm
and
d
HSL act in a synergistic man-
ner. Under starvation conditions, adult
bmm
mutants outlived the controls, appar-
ently owing to the more abundant fat storage prior to starvation.
4.3.3
dSeipin
Seipin, an ER resident protein, was named after a physician, Dr. Seip, who first
reported a few cases of a generalized congenital lipodystrophy in children, along
with Dr. Berardinelli's subsequent reports, that were later defined as Berardinelli-
Seip congenital lipodystrophy 2 (BSCL) (
Berardinelli, 1954; Magre et al., 2001;
Seip & Trygstad, 1963
). Patients with BSCL lack significant adipose tissue and ex-
hibit diverse clinical symptoms such as hepatic steatosis, muscular hypertrophy,
hypertriglyceridemia, and insulin resistance due to ectopic lipid storage (
Magre
