Poster Topical Area: Nutrient-Gene Interactions

Location: Hall D

Poster Board Number: 427

P17-004 - Dark chocolate consumption can differentially modulate human gene expression for T cell activation, cellular immune response, neural signaling, and sensory perception

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives: Map the impact of 70% cocoa consumption on human immune and dendritic cell gene expression, with focus on pro/anti-inflammatory cytokines.

Methods: This pilot study enrolled 4 subjects (2 f/ 2 m, age 25-50) and 1 control (f, 28). After a baseline blood draw, subjects consumed 70% cocoa over 10 min (antioxidant activity (aa), 46,000 μmoles TE/100g). Follow-up samples were obtained post- 2 h and 1 wk. Subjects consumed 48 g 70% cocoa/day (2 pieces/h; aa 3834 μmoles TE/100g). Total RNA was assayed by RNAseq, with data analyzed by linear models to identify differentially expressed genes, followed by bioinformatic analyses of transcription control pathways and cellular origins.

Results: Leukocyte transcriptome profiles showed little systematic change in the initial 2 h of cocoa exposure, although pre-specified bioinformatics analyses indicated small increases in activity of genes regulated by NF-kB and AP1 transcription factors and CD4+ and CD8+ T cells (all, p < .05). By contrast, analyses of change from baseline to 1 wk identified 177 genes showing significant differential expression using a priori-specified False Discovery Rate cut-point of .20 (140 up-regulated, 37 down-regulated), with 116 achieving q < .05. Up-regulated genes were involved in leukocyte activation and motility (CD40, TICAM2, AZU1, HRAS and RASD2, HSPA1L, FGF22); derived from CD4+ and CD8+ T lymphocytes (p < .001 and .0148); and showed over-representation of promoter elements for NF-kB, SP-1, MZF-1, and HIF-1 transcription factors (all p < .01) and under-representation of AP-1 (p = .018). Up-regulated transcripts also included genes involved in neural signaling and sensory perception (OR2J3, OR52A5, OR6C3, OR9I1, NR4A2, and NRXN2).

Conclusion: Cocoa consumption up-regulates multiple intracellular signaling pathways involved in T cell activation and cellular immune response. Results are consistent with previous indications that cocoa components inhibit MAPK activation, but suggest T cell function may be preserved and enhanced via other compensatory molecular pathways. It should be noted that the NF-kB up-regulation source was not from up-regulated monocytes suggesting a role other than cascading inflammation. It is of interest, to note, that genes involved in neural signaling and sensory processes were up-regulated.

Funding Source: Departmental
Cocoa & Gene Expression

CoAuthors: Kristin Bruhjell, BS – Loma Linda University Health; Warren Peters, MD, MPH – Loma Linda University Health; Peter Bastian, MD – Loma Linda University Health; Everett Lohman, DPT, DSc – Loma Linda University Health; Gurinder Bains, MD, PhD – Loma Linda University Health; Jesusa Arevalo – UCLA School of Medicine ; Steve Cole, PhD – UCLA School of Medicine

Lee Berk

Associate Dean for Research Affairs, School of Allied Health Professions
Loma Linda University Health
Loma, California