Hormone-sensitive Lipase Deficiency in Mice Causes Diglyceride Accumulation in Adipose Tissue, Muscle, and Testis*

By G. Haemmerle, R. Zimmermann, M. Hayn, Christian Theussl, G. Waeg, E. Wagner, W. Sattler, T. Magin, E. Wagner, R. Zechner. Journal of Biological Chemistry, 2002

616 citations recorded by the source corpus.

Hormone-sensitive lipase (HSL) is expressed predominantly in white and brown adipose tissue where it is believed to play a crucial role in the lipolysis of stored triglycerides (TG), thereby providing the body with energy substrate in the form of free fatty acids (FFA). From in vitro assays, HSL is known to hydrolyze TG, diglycerides (DG), cholesteryl esters, and retinyl esters. In the current study we have generated HSL knock-out mice and demonstrate three lines of evidence that HSL is instrumental in the catabolism of DG in vivo. First, HSL deficiency in mice causes the accumulation of DG in white adipose tissue, brown adipose tissue, skeletal muscle, cardiac muscle, and testis. Second, when tissue extracts were used in an in vitro lipase assay, a reduced FFA release and the accumulation of DG was observed in HSL knock-out mice which did not occur when tissue extracts from control mice were used. Third, in vitro lipolysis experiments with HSL-deficient fat pads demonstrated that the isoproterenol-stimulated release of FFA was decreased and DG accumulated intracellularly resulting in the essential absence of the isoproterenol-stimulated glycerol formation typically observed in control fat pads. Additionally, the absence of HSL in white adipose tissue caused a shift of the fatty acid composition of the TG moiety toward increased long chain fatty acids implying a substrate specificity of the enzymein vivo. From these in vivo results we conclude that HSL is the rate-limiting enzyme for the cellular catabolism of DG in adipose tissue and muscle.

Subfields: Biochemistry, Cell Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/a9e96cf37388805aa5ed529dfb03d2bac2e158a7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. R. Zechner
2. Sally Martin
3. Robert G. Parton
4. Frank Madeo

In Cell Biology

1. Robert G. Parton
2. Elina Ikonen
3. C. Dart
4. Berislav Zlokovic

In Physiology

1. R. Zechner
2. R. Zimmermann
3. Robert G. Parton
4. A. Lass
5. C. Dart

Citations in the corpus

• Opinion: Lipid droplets: a unified view of a dynamic organelle (2006, background): “It was only following the observation that lipolysis was not ablated in mice after the targeted gene disruption of HSL that the presence of other lipolytic enzymes was propose”
• ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1 (2011, background): “The relatively benign phenotype of Hsl deficiency in mice ( Hsl -knockout mice, hereafter referred to as Hsl KO) argues against a crucial role of this enzyme in the regulation of PPARs and energy homeostasi”
• Regulation of lipolysis in adipocytes. (2007, positive): “To address the functional role of HSL in vivo, several laboratories generated HSL-null mouse models (44,94,134).”
• Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores (2011, background): “Adipocytes of HSL-deficient mice exhibit only a moderate decrease in stimulated lipolysis [11,21].”
• Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. (2006, background): “Yet, studies in HSL-deficient mice showed that the enzyme is rate limiting in vivo for the catabolism of DG but not for TG (Haemmerle et al., 2002).”