Cholesterol Homeostasis and Diabetes

Hormone-sensitive lipase (HSL) is widely expressed in adipose tissue. Interestingly, HSL-null mice have been shown to be resistant to diet-induced obesity. Despite this characteristic, they can also show insulin resistance. This resistance is contributing factor in type 2 diabetes.

Scientists have also shown that pancreatic beta cells, responsible for insulin release, begin to malfunction when their cholesterol levels build up. So what is the link?

The study referenced here suggests that HSL plays a critical role in the hydrolysis of cytosolic cholesteryl esters and that increased levels of hepatic cholesteryl esters, due to lack of action of HSL in the liver, is the main mechanism underlying the imbalance in cholesterol metabolism in HSL-null mice.

Celine Fernandez, Marie Lindholm, Morten Krogh, Stéphanie Lucas, Sara Larsson, Peter Osmark, Karin Berger, Jan Boren, Barbara A Fielding, Keith N. Frayn and Cecilia Holm. Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice. Am J Physiol Endocrinol Metab (July 29, 2008). doi:10.1152/ajpendo.90206.2008.

...Liver samples were homogenized in lysis buffer pH 7.0 containing 25 mM Tris, 150 mM NaCl, 1 mM EDTA, 1% Triton and 1X protease inhibitor cocktail (Complete Mini, Roche). Total protein concentration was measured by BCA assay (Pierce) and 50 μg of protein were subjected to SDS-polyacrylamide gel electrophoresis (8 % polyacrylamide). After transfer to PVDF membranes (Invitrogen), blots were incubated with a primary antibody mouse anti-mouse/rat ABCA1 (Neuromics) according to the instructionsof the manufacturer. As secondary antibody a horseradish peroxidase-conjugated sheep antimouse IgG was used. Western blot analysis was performed using a chemiluminescence system (Luminol) and detection was made using a CCD-camera (LAS 1000, Fuji). Band intensities were quantified using the ImageJ software (http://rsb.info.nih.gov/ij)...