Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle
Authors: Guenter Haemmerle
Gabriele Knipping
Rudolf Zechner
Robert Zimmermann
Dagmar Kratky
Monika Riederer
Juliane G Strauss
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hormone-sensitive lipase; lipolysis; triglycerides; non-esterified fatty acids; plasma lipids
Affiliations: Institute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Heinrichstrasse 31a, Graz A-8010, Austria.

Abstract:  Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile. 

Retracted: No

PubPeer comments:
 It seems that the authors repeatedly used the loading control with slightly different brightness and contrast for figure 7, which is more evident in the pseudo color mode. These loading controls share the same features but in the figure depicted to represent different tissues. Could authors provide original images?   , 
 This figure shows a qualitative comparison (without quantitation or statistics!) of LPL expression in white adipose tissue, brown adipose tissue, and cardiac muscle tissue from HSL-expressing (wt) and HSL-deficient (ko) mice. In the bottom panel of this figure showing an ethidium bromide stained RNA agarose gel, the gel image of a white adipose tissue sample is shown twice (next to RNA from cardiac muscle tissue). Instead of this duplication, tissue samples from different adipose tissue depots (white fat and brown fat) should have been shown. Unfortunately, after more than 20 years and several changes of the gel documentation system, we were unable to unearth the original data. But reconstructing the work flow, we know that the ethidium bromide-stained agarose gel was photographed before the blotting experiment. Subsequently, the photograph was scanned and those samples of the image that were relevant for the publication were rearranged and are presented in Fig.7 as loading and quality control of the RNA samples. We suspect that during this process, the mistake of inserting the same image twice must have happened (with slightly different background intensities in the images). Although this double presentation of RNA samples from the same adipose tissue represents a regrettable error, it did not affect the actual Northern blotting result (upper panel). Here, the samples are correctly designated and accurately show distinct data obtained for the three tissue types. Since the qualitative assessment of the signal strengths in the Northern blot can be related to the total mass of RNA applied to the gel (10 uf06dg per gel-lane), the qualitative results obtained from the blotting experiment are still valid and can be interpreted independently of the ethidium bromide visualized bands. Moreover, the result that HSL deficiency does not affect the expression of LPL mRNA in adipose tissue and myocardium was confirmed in a later study by the group of Z. Trajanoski (Pinent et al. Genomics. 2008, doi: 10.1016 j.ygeno. 2008.03.010). ,