AN
2006:175 DISSABS Order Number: AAIC821247 (not available for sale by
UMI)
TI
Hormone-sensitive lipase: New roles for an old enzyme
AU
Hansson, Ola Axel [Ph.D.]
CS
Lunds Universitet (Sweden) (0899)
SO
Dissertation Abstracts International, (2005) Vol. 66, No. 4C, p. 766.
Order No.: AAIC821247 (not available for sale by UMI). 147 pages.
ISBN: 91-85439-76-2.
DT
Dissertation
FS
DAI
LA
English
ED
Entered STN: 20060126
Last Updated on STN: 20060126
AB
Hormone-sensitive lipase (HSL) has a unique ability to
hydrolyze a large panel of substrates including acylglycerols, cholesteryl
esters and retinyl esters. HSL is potentially a new drug target for the
treatment of obesity and type II diabetes. However, as HSL is not only
expressed in white adipose tissue (WAT), but also plays significant roles
in other tissues, it is of importance to better understand the different
functions of this enzyme in the body.
In this thesis the aim has been to study the consequences of a
targeted disruption of the HSL gene in the mouse with focus on the
effects in skeletal muscle and WAT.
Expressional and functional analyses of soleus muscle of HSL null
mice suggests an important role of HSL in skeletal muscle metabolism as
the absence of HSL leads to increased glycogen utilization and an
increased amount of lipid droplets, which presumably reflects a metabolic
switch from lipid to carbohydrate metabolism.
A fibre type transformation from slow twitch oxidative fibres to an
enrichment of fast twitch glycolytic fibres in soleus muscle is also
suggested.
Using a proteomic approach a local inflammatory response in WAT is
demonstrated in the non-obese HSL null mouse model. New methodological
aspects of analysing data generated by two-dimensional polyacrylamide gel
electrophoresis are also presented. Increased energy expenditure and
perturbation of adipogenesis are suggested reasons behind the observed
protection against diet-induced obesity in HSL null mice. Results
presented in this thesis suggest an important role of HSL in lipid
signalling and adipogenesis through its action as a retinyl ester
hydrolyze in WAT.
CC
0379 BIOLOGY, CELL; 0487 CHEMISTRY, BIOCHEMISTRY; 0571 HEALTH SCIENCES,
PATHOLOGY