Targeting of Acyl-CoA synthetase 5 decreases jejunal fatty acid activation with no effect on dietary long-chain fatty acid absorption. 2013

Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
Genomic Medicine Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA.

BACKGROUND The absorption of dietary long chain fatty acids (LCFA) largely occurs in the jejunum. LCFA are activated via conjugation with Coenzyme A (CoA), a reaction catalyzed by Acyl-CoA synthetases (ACS). Acyl-CoA sythesis is critical for dietary LCFA absorption; yet, the jejunal ACS enzymes that catalyze the reaction are largely unknown. RESULTS High throughput mRNA sequencing of the mouse jejunum revealed that the expression of acyl-CoA synthetase 5 (Acsl5) and fatty-acid transport protein 4 (Fatp4) largely exceeded all other annotated ACS genes that activate LCFA. Interestingly, Acsl5 knockout (KO) mice displayed a decrease of 60% in jejunal total long chain acyl-CoA synthesis rate. Nevertheless, and despite of this decrease, dietary LCFA absorption and body-weight gain in response to high fat diet remained unaffected. CONCLUSIONS Acsl5 is a major activator of dietary LCFA, yet in Acsl5 KO mice residual ACS activity is sufficient for maintaining a normal LCFA absorption. Our findings provide further evidence for a robust small intestine LCFA absorption capacity.

UI MeSH Term Description Entries
D007583 Jejunum The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Jejunums
D003065 Coenzyme A CoA,CoASH
D003066 Coenzyme A Ligases Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1. Acyl CoA Synthetase,Acyl CoA Synthetases,Acyl Coenzyme A Synthetase,Acyl Coenzyme A Synthetases,Coenzyme A Ligase,Coenzyme A Synthetase,Coenzyme A Synthetases,Acid-Thiol Ligases,Co A Ligases,A Ligase, Coenzyme,A Synthetase, Coenzyme,Acid Thiol Ligases,CoA Synthetase, Acyl,CoA Synthetases, Acyl,Ligase, Coenzyme A,Ligases, Acid-Thiol,Ligases, Co A,Ligases, Coenzyme A,Synthetase, Acyl CoA,Synthetase, Coenzyme A,Synthetases, Acyl CoA,Synthetases, Coenzyme A
D004032 Diet Regular course of eating and drinking adopted by a person or animal. Diets
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D050612 Fatty Acid Transport Proteins A broad category of membrane transport proteins that specifically transport FREE FATTY ACIDS across cellular membranes. They play an important role in LIPID METABOLISM in CELLS that utilize free fatty acids as an energy source. Fatty Acid-Transport Protein,Fatty Acid Transport Protein
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059014 High-Throughput Nucleotide Sequencing Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc. High-Throughput Sequencing,Illumina Sequencing,Ion Proton Sequencing,Ion Torrent Sequencing,Next-Generation Sequencing,Deep Sequencing,High-Throughput DNA Sequencing,High-Throughput RNA Sequencing,Massively-Parallel Sequencing,Pyrosequencing,DNA Sequencing, High-Throughput,High Throughput DNA Sequencing,High Throughput Nucleotide Sequencing,High Throughput RNA Sequencing,High Throughput Sequencing,Massively Parallel Sequencing,Next Generation Sequencing,Nucleotide Sequencing, High-Throughput,RNA Sequencing, High-Throughput,Sequencing, Deep,Sequencing, High-Throughput,Sequencing, High-Throughput DNA,Sequencing, High-Throughput Nucleotide,Sequencing, High-Throughput RNA,Sequencing, Illumina,Sequencing, Ion Proton,Sequencing, Ion Torrent,Sequencing, Massively-Parallel,Sequencing, Next-Generation

Related Publications

Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
November 2013, World journal of gastroenterology,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
June 1963, Biochimica et biophysica acta,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
January 2016, Methods in molecular biology (Clifton, N.J.),
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
November 2010, Journal of lipid research,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
October 2013, The Journal of nutritional biochemistry,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
October 2009, The Journal of biological chemistry,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
January 1975, Methods in enzymology,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
July 1998, The Journal of biological chemistry,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
December 1999, The Journal of biological chemistry,
Nahum Meller, and Michelle E Morgan, and Winifred Ps Wong, and Jessica B Altemus, and Ephraim Sehayek
January 1981, FEBS letters,
Copied contents to your clipboard!