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

• Published in: Lipids in health and disease Vol. 12; no. 1; p. 88
• Main Authors: Meller, Nahum, Morgan, Michelle E, Wong, Winifred Ps, Altemus, Jessica B, Sehayek, Ephraim
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.06.2013; BioMed Central
• Subjects: Absorption - genetics; Analysis; Animals; Body weight; Coenzyme A - metabolism; Coenzyme A Ligases - antagonists & inhibitors; Coenzyme A Ligases - metabolism; Diet; Fatty Acid Transport Proteins - metabolism; Fatty acids; Fatty Acids - administration & dosage; Fatty Acids - biosynthesis; Fatty Acids - metabolism; Genes; Health aspects; High-Throughput Nucleotide Sequencing; Jejunum - metabolism; Mice; Mice, Knockout; RNA; RNA sequencing; Short Report; Thiols
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/1476-511X-12-88

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. 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. 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.