Abstract

BackgroundBetel-nut consumption is the fourth most common addictive habit globally and there is good evidence linking the habit to obesity, type 2 diabetes (T2D) and the metabolic syndrome. The aim of our pilot study was to identify gene expression relevant to obesity, T2D and the metabolic syndrome using a genome-wide transcriptomic approach in a human monocyte cell line incubated with arecoline and its nitrosated products.ResultsThe THP1 monocyte cell line was incubated separately with arecoline and 3-methylnitrosaminopropionaldehyde (MNPA) in triplicate for 24 h and pooled cDNA indexed paired-end libraries were sequenced (Illumina NextSeq 500). After incubation with arecoline and MNPA, 15 and 39 genes respectively had significant changes in their expression (q < 0.05, log fold change 1.5). Eighteen of those genes have reported associations with T2D and obesity in humans; of these genes there was most marked evidence for CLEC10A, MAPK8IP1, NEGR1, NQ01 and INHBE genes.ConclusionsOur preliminary studies have identified a large number of genes relevant to obesity, T2D and metabolic syndrome whose expression was changed significantly in human TPH1 cells following incubation with betel-nut derived arecoline or with MNPA. These findings require validation by further cell-based work and investigation amongst betel-chewing communities.

Highlights

  • Betel-nut consumption is the fourth most common addictive habit globally and there is good evidence linking the habit to obesity, type 2 diabetes (T2D) and the metabolic syndrome

  • Determination of concentration of arecoline, MNPA and MNPA and 3methylnitrosaminopropionitrile (MNPN) to be used in cell based assays Cell viability using serial dilutions of arecoline extracts in culture media was assessed by phase contrast light microscopy

  • When THP1 cells are incubated for 48 h or more with arecoline concentrations of either 10 or 50 μg/ml the cells look healthy with similar regular appearance by phase contrast microscopy to controls

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Summary

Introduction

Betel-nut consumption is the fourth most common addictive habit globally and there is good evidence linking the habit to obesity, type 2 diabetes (T2D) and the metabolic syndrome. In the Keelung Community Integrated Screening program from Taiwan, paternal betel-chewing was associated, dose-wise, with increases in early onset metabolic syndrome in their never-chewing offspring, while betel-chewing in adults increased their risks, dose-wise, of early onset T2D, cardiovascular disease and metabolic syndrome [6,7,8] These data in humans support earlier data reported in CD1 mice, where it was found that a proportion of betel-fed adult mice developed hyperglycaemia and obesity and, most remarkably, that amongst their neverbetel-fed offspring hyperglycaemia was detected in up to the 4th generation and that the vertical transmission of hyperglycaemia was associated with paternal, but not maternal, hyperglycaemia [9]

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