Endothelial acyl-CoA synthetase 1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.

Abstract

OBJECTIVE:

Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo.

METHODS AND RESULTS:

Saturated fatty acids caused increased inflammatory activation, endoplasmic reticulum stress, and apoptosis in mouse microvascular endothelial cells. Forced ACSL1 overexpression exacerbated the effects of saturated fatty acids on apoptosis and endoplasmic reticulum stress. However, endothelial ACSL1 deficiency did not protect against the effects of saturated fatty acids in vitro, nor did it protect insulin-resistant mice fed a saturated fatty acid-rich diet from macrophage adipose tissue accumulation or increased aortic adhesion molecule expression.

CONCLUSIONS:

Endothelial ACSL1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.

• Authors: Xin Li, Oscar Gonzalez, Xia Shen, Shelley Barnhart, Farah Kramer, Jenny E Kanter, Anuradha Vivekanandan-Giri, Kyoichiro Tsuchiya, Priya Handa, Subramaniam Pennathur, Francis Kim, Rosalind A Coleman, Jean E Schaffer, Karin E Bornfeldt
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 33 Issue 2 Pg. 232-40 (Feb 2013) ISSN: 1524-4636 [Electronic] United States
• PMID: 23241406 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Acyl Coenzyme A
• Fatty Acids
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Palmitoyl Coenzyme A
• stearoyl-coenzyme A
• JNK Mitogen-Activated Protein Kinases
• ACSL1 protein, mouse
• Coenzyme A Ligases

Topics

• Acyl Coenzyme A (metabolism)
• Adipose Tissue (immunology, metabolism, pathology)
• Animals
• Aorta (metabolism)
• Apoptosis
• Cattle
• Cells, Cultured
• Coenzyme A Ligases (deficiency, genetics, metabolism)
• Disease Models, Animal
• Endoplasmic Reticulum Stress
• Endothelial Cells (enzymology, immunology, pathology)
• Enzyme Activation
• Fatty Acids (metabolism)
• Inflammation (enzymology, immunology, pathology)
• Insulin Resistance
• Intercellular Adhesion Molecule-1 (metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Macrophages (immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Obesity (enzymology, genetics, immunology, pathology)
• Palmitoyl Coenzyme A (metabolism)
• RNA Interference
• Time Factors
• Transfection
• Vascular Cell Adhesion Molecule-1 (metabolism)