Elsevier

Food Chemistry

Volume 228, 1 August 2017, Pages 35-42
Food Chemistry

Aroma compound diacetyl suppresses glucagon-like peptide-1 production and secretion in STC-1 cells

https://doi.org/10.1016/j.foodchem.2017.01.104Get rights and content

Highlights

  • A volatile favour compound with a pleasant aroma supresses GLP-1, a satiety hormone.

  • Aromatic diacetyl recruits GPR120 to the cell surface and increases cAMP levels.

  • K+ATP channels, Ca2+ channels and the α-gustducin taste pathway are not involved.

Abstract

Diacetyl is a volatile flavour compound that has a characteristic buttery aroma and is widely used in the flavour industry. The aroma of a food plays an important role in food palatability and thus intake. This study investigates the effect of diacetyl on the satiety hormone, glucagon-like peptide (GLP-1), using the enteroendocrine cell line, STC-1. Diacetyl decreased proglucagon mRNA and total GLP-1 from glucose stimulated STC-1 cells. This dampening effect on GLP-1 appears to be mediated by increasing intracellular cAMP levels, increasing synthesis of the G protein coupled receptor, GPR120, and its recruitment to the cell surface. Voltage gated Ca2+ channels, K+ATP channels and the α-gustducin taste pathway do not appear to be involved. These findings demonstrate that components contributing to food palatability suppress GLP-1. This ability of diacetyl to reduce satiety signals may contribute to overconsumption of some palatable foods.

Introduction

The gut hormone glucagon-like peptide 1 (GLP-1) has attracted considerable interest in recent years due to its ability to enhance glucose-dependent insulin secretion, promote pancreatic β-cell proliferation and reduce food intake. It has also been reported that GLP-1 may reduce the rewarding and reinforcing properties of palatable foods (Dickson et al., 2012). Secretion of this nutrient-responsive hormone is impaired in obesity and type 2 diabetes (Toft-Nielsen et al., 2001) and infusion of GLP-1 has been shown to improve glycemia and reduce food intake in obese patients (Nauck et al., 1998).

GLP-1 is produced by L cells of the distal jejunum and ileum following tissue-specific proteolytic processing of the proglucagon gene (Baggio & Drucker, 2007). The arrival of carbohydrate, fat and protein in the gut lumen triggers GLP-1 release (Bruen, O'Halloran, Cashman, & Giblin, 2012). Inhibition of GLP-1 by food has not been extensively studied. Within the L cells, GLP-1 secretion occurs in response to an increase in intracellular levels of cyclic adenosine monophosphate (cAMP) and Ca2+ (Tolhurst, Reimann, & Gribble, 2009). Changes in these mediators are brought about by nutrient uptake pathways, metabolic closures of potassium channels and/or activation of nutrient-responsive G protein-coupled receptors (GPCRs) (Reimann et al., 2012). These GPCRs play various roles in GLP-1 secretion. The taste GPCRs, T1r3/T1r2, and the G protein α-gustducin are involved in the secretion of GLP-1 in response to sugars (Jang et al., 2007). On the other hand, free fatty acids (FFA) can induce GLP-1 secretion via the GPCRs, GPR40 and GPR120 (Hirasawa et al., 2005, Reimann et al., 2012). GPR120 is highly expressed in enteroendocrine L cells (Anbazhagan et al., 2016, Hirasawa et al., 2005) and is activated in response to unsaturated long-chain FFA (Tanaka et al., 2008). Recent evidence also suggests that GPR120 plays an important role in the orosensory detection and preference for fats (Cartoni et al., 2010). GPR120 is classified as a Gq/11-coupled receptor, capable of increasing GLP-1 secretion via phospholipase Cβ and intracellular Ca2 signalling (Blad, Tang, & Offermanns, 2012) although there is also some evidence of signalling promiscuity (Reimann et al., 2012, Tsukahara et al., 2015).

Whilst the role of taste receptors and tastants in GLP-1 secretion has been widely investigated in recent years, there is less information available on whether aromatic compounds may also influence satiety signals. The aroma of a food plays an important role in food palatability and intake (Massolt et al., 2010, Ruijschop et al., 2009). Whilst such effects may be mediated through neural pathways, it is also possible that aroma compounds may influence satiety signals. Indeed, it has been demonstrated that food-derived odorants present in the gut lumen may stimulate serotonin release via olfactory receptors present in human enterochromaffin cells (Braun, Voland, Kunz, Prinz, & Gratzl, 2007) and aroma intensity certainly influences perceived satiation (Ruijschop et al., 2009).

Diacetyl (2,3-butanedione) is a volatile favour compound that occurs naturally in several foods, such as butter, milk, cheese, fruit and coffee and has a characteristic buttery aroma (Bartowsky & Henschke, 2004). It is primarily produced by citrate fermenting lactic acid bacteria during pyruvate metabolism. It is widely used in the flavouring industry. This pleasant buttery aroma is perceived as a positive attribute by consumers and has been shown to play a significant role in food preference and palatability (Liggett, Drake, & Delwiche, 2008).

The present study was undertaken to evaluate whether diacetyl alters GLP-1 production and secretion, using the murine secretin tumor cell line, STC-1. STC-1 is a popular and reliable enteroendocrine model to investigate gut hormone production and secretion. Similar to native L cells, STC-1 cells secrete GLP-1 in response to sugars, peptides, fatty acids, sweeteners, bitter tastants, food bioactives, hormones and bile (McCarthy et al., 2015). However levels of response may differ to the native state (Kuhre et al., 2016). STC-1 cells also express GPR120, taste receptors (T1r1, T1r2, T1r3) and α-gustducin (Hirasawa et al., 2005, Wu et al., 2002) and are recognized as a good model for taste signalling (Saitoh, Hirano, & Nishimura, 2007).

Section snippets

Chemicals

Diacetyl, KREBS ringers bicarbonate buffer, nicardipine, nitrendipine, tolbutamide, pertussis toxin, polyethylene glycol, DMSO, Hanks Balanced Salt Solution, DMEM media, glucose, L-glutamine, foetal bovine serum, penicillin, streptomycin, 3-Isobutyl-1-methylxanthine (IBMX), forskolin, poly-l-lysine coated glass-slides, paraformaldehyde, HEPES, NaCl, EDTA, ethylene glycol tetraacetic acid, Nonident P40, dithiothreitol, Na3VO4, phenylmethysulphonyl fluoride, aprotinin, leupeptin, NaF, NaPPi,

Diacetyl reduces proglucagon mRNA levels and total GLP-1 secretion in the presence of 10mM glucose

STC-1 cells were exposed to physiologically relevant concentrations of the volatile flavour compound, diacetyl. As in other studies (Zhou & Pestka, 2015), exposures were performed in the presence of the known stimulator, glucose. In our study, experiments were performed in KREBS Ringers bicarbonate buffer, which contains 10 mM glucose. Exposure of STC-1 cells to diacetyl resulted in a significant (P < 0.05) dose-dependent decrease in proglucagon mRNA levels compared to the vehicle control at all

Discussion

The widely used flavour ingredient diacetyl inhibits production and secretion of GLP-1 by intestinal endocrine cells in vitro. This damping effect on GLP-1 appears to be mediated by recruiting GPR120 to the cell surface, increasing intercellular cAMP levels and increasing GPR120 synthesis. The mechanism of GLP-1 reduction by diacetyl appears to be electroneutral, as evidenced by independence from K+ATP channels and voltage-gated Ca2+ channels. The α-gustducin taste pathway also does not appear

Acknowledgements

T. McCarthy was in receipt of a Teagasc Walsh Fellowship. This work was funded by Enterprise Ireland under Grant Number CC20080001. We would like to thank John Hannon for technical assistance using the volatile compound, diacetyl.

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