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Molecular mechanisms regulating hormone-sensitive lipase and lipolysis
1Department of Cell and Molecular Biology, Section for Molecular Signalling, Lund University, Lund, Sweden. cecilia.holm@medkem.lu.se
Biochemical Society Transactions
|December 4, 2003
Summary
Hormone-sensitive lipase (HSL) is crucial for fatty acid release. HSL-null mice show impaired insulin sensitivity in multiple tissues, indicating HSL
Area of Science:
- Biochemistry
- Metabolism
- Endocrinology
Background:
- Hormone-sensitive lipase (HSL) is a key enzyme regulating fatty acid mobilization from acylglycerols.
- Catecholamines stimulate lipolysis via protein kinase A (PKA)-mediated phosphorylation of HSL and perilipin in adipocytes.
- Insulin's anti-lipolytic effect is mediated by phosphodiesterase 3B, reducing cAMP levels.
Purpose of the Study:
- To investigate the role of HSL in lipolysis and insulin sensitivity.
- To characterize the function of PKA phosphorylation sites on HSL.
- To analyze the metabolic phenotype of HSL-null mice.
Main Methods:
- Generation and analysis of homozygous HSL-null mice.
- Measurement of glycerol and fatty acid release from adipocytes.
- Assessment of insulin sensitivity through glucose tolerance and insulin tolerance tests.
Main Results:
- HSL-null adipocytes exhibited blunted catecholamine-induced glycerol and reduced fatty acid release.
- HSL-null mice displayed basal hyperinsulinaemia and impaired glucose disposal.
- Insulin resistance was observed in the liver, adipose tissue, and skeletal muscle of HSL-null mice.
Conclusions:
- HSL is essential for catecholamine-stimulated lipolysis.
- HSL deficiency leads to systemic insulin resistance in mice.
- Additional lipases contribute to basal and stimulated lipolysis in adipocytes.