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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Nagy, HM; Paar, M; Heier, C; Moustafa, T; Hofer, P; Haemmerle, G; Lass, A; Zechner, R; Oberer, M; Zimmermann, R.
Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A.
Biochim Biophys Acta. 2014; 1841(4):588-594
Doi: 10.1016/j.bbalip.2014.01.005
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Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Hofer Peter
- Hofer Philipp
- Moustafa Tarek
- Paar Margret
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- Abstract:
- Adipose triglyceride lipase (ATGL) is required for efficient mobilization of triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore, ATGL strongly determines the availability of fatty acids for metabolic reactions. ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic hormones. These signals control enzyme expression and the interaction of ATGL with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether ATGL activity is also controlled by lipid intermediates generated during lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs in a non-competitive manner, similar as previously shown for hormone-sensitive lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs, diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays revealed that acyl-CoAs do not disrupt the protein-protein interaction of ATGL and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of the presence of CGI-58 and occurs directly at the N-terminal patatin-like phospholipase domain of the enzyme. In conclusion, our results suggest that inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs could represent an effective feedback mechanism controlling lipolysis and protecting cells from lipotoxic concentrations of fatty acids and fatty acid-derived lipid metabolites. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- 1-Acylglycerol-3-Phosphate O-Acyltransferase - metabolism
- Acyl Coenzyme A - genetics
- Acyl Coenzyme A - metabolism
- Adipose Tissue - enzymology
- Cell Cycle Proteins - metabolism
- Fatty Acids - metabolism
- Humans -
- Lipase - antagonists & inhibitors
- Lipase - genetics
- Lipase - metabolism
- Lipid Metabolism -
- Lipolysis - genetics
- Sterol Esterase - antagonists & inhibitors
- Sterol Esterase - genetics
- Sterol Esterase - metabolism
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- Adipose triglyceride lipase
- Hormone-sensitive lipase
- Lipolysis
- Regulation
- acyl-CoA