High incorporation of long‐chain fatty acids contributes to the efficient production of acylated ghrelin in ghrelin‐producing cells

Abstract

Edited by L aszl o NagyThe mechanisms for supplying octanoic acid for ghrelin acylation in X/A-like cells are incompletely understood. We found that long-chain fatty acids were incorporated at a higher rate in the ghrelin-producing cell line MGN3-1 than in MIN6 cells, in part due to higher expression level of long-chain fatty acylCoA synthetase family member 1 (Acsl1). Inhibition of ACSLs by triacsin C profoundly suppressed acylated ghrelin production. These results suggest that high incorporation of long-chain fatty acids into the ghrelin-producing cells plays a role in the supply of octanoic acid for ghrelin acylation.

Human gastrointestinal epithelia of the esophagus, stomach, and duodenum resolved at single-cell resolution

“…Next, we searched for EEC subtype-enriched gene expression signatures in the ghrelin (GHRL)-producing gastric X cells and duodenal MX cells (Figure 5C). Both cell types share the expression of 18 genes, including ACSL1 encoding the long-chain fatty-acid-coenzyme A (CoA) ligase required for acetyl modification of GHRL (Bando et al, 2016;Beumer et al, 2020) and NPY1R encoding the receptor for the neuropeptides NPY and PPY that may modulate the activity of both X and MX cells (Figure 5C). The gastric X cell-enriched expression signature consisted of 10 genes, which included the genes encoding CFC1, a member of the epidermal growth factor family, and the free fatty acid receptor FFAR3 sensing short fatty acids in the gut lumen (Figure 5C).…”

Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis

“…These cells were selected for our study because they express CB 1 R (Koyama et al, 2016), similar to primary gastric mucosal cells (Engelstoft et al, 2013). Additionally, they are capable of incorporating and metabolizing long-chain fatty acids to generate octanoic acid for ghrelin acylation, unlike some other ghrelin-producing cell lines that require octanoic acid supplementation to produce octanoylghrelin (Bando et al, 2016).…”

Membrane Disruption by Very Long Chain Fatty Acids During Necroptosis

“…We note that Compound V alone induces toxicity at 50 µM concentration and if we scale the viability of Compound V treated cells to 100%, the Compound V-treated necroptotic cells show 59% viability relatively, further supporting that Compound V protects against cell death during necroptosis. Similarly, inhibiting acyl-CoA synthetase activity by Triacsin C [40][41] resulted in a significant increase in cell viability during necroptosis, suggesting activation of fatty acids is involved in necroptotic cell death (Figure S6).…”