title: Targeting of Acyl-CoA synthetase 5 decreases jejunal fatty acid activation with no effect on dietary long-chain fatty acid absorption.
abstract: 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.
authors.affiliation: Genomic Medicine Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA.
authors.forename: Nahum
authors.initials: N
authors.lastname: Meller
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Morgan
authors.forename: Winifred Ps
authors.initials: WP
authors.lastname: Wong
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Altemus
authors.forename: Ephraim
authors.initials: E
authors.lastname: Sehayek
mesh_terms: D000042:Absorption / Q000235:genetics; D000818:Animals; D003065:Coenzyme A / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004032:Diet; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
chemical_list: D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; C493572:Slc27a4 protein, mouse; D003066:Coenzyme A Ligases; C115795:acyl CoA synthetase 5; D003065:Coenzyme A