Short‐chain fatty acids increase intracellular calcium levels and enhance gut hormone release from STC‐1 cells via transient receptor potential Ankyrin1

Abstract

Short‐chain fatty acids (SCFAs), metabolites of colonic bacterial fermentation of complex carbohydrates, are closely related to the release of gut hormones. In this study, we examined the involvement of transient receptor potential ankyrin 1 (TRPA1) in SCFA‐induced increase in intracellular calcium ([Ca2+]i) and its impact on gut hormone secretion using naturally TRPA1 expressing intestinal secretin tumour cell‐1 (STC‐1) cell line. Individual SCFAs and their physiological mix enhanced calcium influx in TRPA1‐dependent manner. SCFA mix also significantly increased membrane expression of TRPA1. Gene expression studies revealed that SCFA mix elevated the expression of genes involved in calcium‐activated calcineurin pathway in TRPA1‐dependent manner and cAMP‐regulated transcriptional co‐activators (CRTC) pathway independent to TRPA1. Genes representing synaptic vesicular exocytosis and gut hormone precursors were significantly elevated with SCFA mix treatment. Treatment with TRPA1 antagonist HC‐030031 markedly reduced these effects. The release of gut hormones was elevated with 10 mm SCFA mix in TRPA1 dependent manner. Our in vivo prebiotic study results suggested presence of an environment conducive to increase in gut hormone secretion. Overall, our findings provide an evidence for the possible role of TRPA1 in SCFA‐induced increase in gut hormone secretion, hence another mechanism of action for prebiotics.

Capsazepine-Induced Altered Colonic Mucosal Health Limits Isomalto-oligosaccharide Action in High-Fat Diet-Fed C57BL/6J Mice

“…Some bacterial strains (Lactobacillus, Bacteroides, Fecalibacterium, Anaerostipes butyraticus) modulate the goblet cell differentiation and stimulate mucus production. ,− Their persistently low abundances, in HFD and HFD + CPZ and HFD + CPZ + IMO groups, might also be impeding the improvement in mucus production. On the other hand, the positive influence of prebiotics on gut microbiota ,− supports our observation of increase in abundance of commensal bacteria in the HFD + IMO group. The increase in mucin-producing bacteria such as Lactobacillus, Anaerostipes butyraticus, and Bacteroides, as well as bacteria that degrade mucus, such as Akkermansia muciniphila and Bacteroides ,,, in the HFD + IMO group suggests a positive effect of IMO in preventing HFD-induced complications.…”

Effect of Single Oral Coingestion of GABA and Malic Acid on Postprandial GLP‐1, Glucose, and Insulin Responses in Healthy Volunteers: A Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study

“…[ 28 ] Another study reported that short‐chain fatty acids, which are organic acids, increase intracellular Ca 2+ levels and enhance GLP‐1 release from STC‐1 cells via transient receptor potential Ankyrin 1. [ 29 ] In the present study, the combined with GABA and MA synergistically increased [Ca 2+ ] i . Because intracellular Ca 2+ acts as a key second messenger in the release of peptide hormones, we reasoned that MA‐dependent changes in [Ca 2+ ] i may play a synergistic role in GLP‐1 secretion with GABA.…”

Intrarectal Capsazepine Administration Modulates Colonic Mucosal Health in Mice

“…Short-chain fatty acids (SCFAs), the enterosyne released from anaerobic bacterial fermentation of dietary substrates (mainly prebiotic containing indigestible carbohydrates) [ 19 , 20 , 21 ], possess gut modulatory properties. They are significantly involved in the maintenance of colonic mucus production, intestinal barrier integrity, and also have anti-inflammatory and immunomodulatory properties [ 22 , 23 , 24 , 25 ].…”