Abstract
BackgroundThe 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.FindingsHigh 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.ConclusionAcsl5 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.
Highlights
The absorption of dietary long chain fatty acids (LCFA) largely occurs in the jejunum
Acsl5 is a major activator of dietary LCFA, yet in Acsl5 KO mice residual Acyl-CoA synthetases (ACS) activity is sufficient for maintaining a normal LCFA absorption
A previous study has shown that fatty-acid transport protein 4 (Fatp4) is pp reads/mRNA nucleotides dispensable for dietary fat absorption [6], we focused our efforts on elucidating the role of Acsl5
Summary
Intestinal absorption of dietary long chain fatty acids (LCFA) is an important determinant of body weight and obesity-related metabolic disorders. LCFA absorption largely occurs in the jejunum where these nutrients undergo uptake across the brush border membrane of enterocytes. LCFA uptake is followed by a critical activation step through conjugation with coenzyme-A (CoA). Dietary LCFA-CoA conjugates are primarily utilized for triglycerides (TG) synthesis, packed into chylomicrons and secreted through the basolateral membrane [1,2]. LCFA conjugation with CoA is catalyzed by Acyl-CoA synthetases (ACS). Mammals possess 13 annotated ACS genes that activate LCFA and clustered in three different gene families: ACSL (acyl-CoA synthetase long chain),. The impact of each of these genes on intestinal absorption of LCFA is largely unknown
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