A special issue on nutritional epigenetics

By: James V. Kohl | Published on: May 10, 2015

See also: Retinoic acid + one receptor regulate the genome
Two decades of scientific progress link what we detailed about RNA-mediated cell type differentiation in our 1996 review: From Fertilization to Adult Sexual Behavior.  Others have begun to learn more about the biological basis of ecological adaptations that link nutrient uptake to the pheromone-controlled physiology of reproduction in all vertebrates by the conserved molecular mechanisms of biophysically constrained RNA-mediated amino acid substitutions and the chemistry of protein folding.
For example, after a request, I submitted this invited review on nutritional epigenetics. Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.  Here is a 5.5 minute video representation of some of what was included in the submission: Nutrient-dependent / Pheromone-controlled thermodynamics and thermoregulation. Obviously, what is known about metabolic networks and genetic networks must link thermodynamic cycles of protein biosynthesis and degradation to organism-level thermoregulation.  For another example of how this occurs in the context of the nutrient-dependent pheromone-controlled GnRH-directed physiology of reproduction in all vertebrates, see: Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling
Others have since linked nutrient-dependent microRNAs from vitamin A and retinoic acid to RNA-directed DNA methylation and RNA-mediated amino acid substitutions via one receptor. This links the receptor to behavior via cell type differentiation in insects and it links the receptor to cell type differentiation in all vertebrates via GnRH.
If you know any reviewers who might be willing to review a submission that links what is currently known about nutritional epigenetics to ecological adaptations, which link the biophysically constrained chemistry of RNA-mediated protein folding to cell type differentiation in all genera via the finely tuned balance of viral microRNAs and nutrient-dependent microRNAs that stabilize the organized genomes of all genera via RNA-mediated amino acid substitutions, please tell me who they are.
The editors of the special issue about nutritional epigenetics in “Nutrients” reported that they couldn’t find anyone who would review my invited submission. Subsequently, a series of articles were been published that separately include the information from my submission without attribution to any of my published works.
By separating the published work on insect polyphenisms from what is known about DNA methylation and the interaction among epigenetics, nutrition, and the development of cancer, the editors of the special issue failed to link what is known about the spatial organization of chromosomes from nutrient-dependent microRNAs and RNA-mediated metabolic networks that link DNA repair to genetic networks via what is known about nutritional epigenetics and pharmacogenomics. For example of separate works that could have been integrated into a comprehwnsive review and a model of how top-down causation is linked to RNA-mediated ecological adaptions, see these articles from the “Special Issue Nutritional Epigenetics” and my comments.
What Do Studies of Insect Polyphenisms Tell Us about Nutritionally-Triggered Epigenomic Changes and Their Consequences?
Concluding sentence:

Further studies of this kind focusing on the role of epigenetics in insect polyphenisms may provide the key basic biology that unlocks our understanding of, and intervention in, diet induced human conditions.

My comment: In my 2012 review, I concluded: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).
Nutrients Intake Is Associated with DNA Methylation of Candidate Inflammatory Genes in a Population of Obese Subjects
Concluding sentence:

Further studies using larger sample sizes and a genome-wide approach are warranted to help increase our understanding of the complex relationship among food intake, oxidative stress and DNA methylation.

My comment: See also: RNA-mediated epigenetic regulation of gene expression

Embedded in the RNA-dependent DNA methylation pathway are important self-reinforcing feedback mechanisms that have been discovered only lately.

The Interaction between Epigenetics, Nutrition and the Development of Cancer (co-author: Lynnette Ferguson)

…it is imperative to understand the implications of diet on epigenetic modifications, and the effect of those modifications on the development of cancer today and in future generations. Such an understanding and an appropriate resultant response would help decrease the level of risk in future generations.

My comment: See also: Combating Evolution to Fight Disease

Deep understanding of the mechanisms that generate variation at the molecular level invites the possibility of fundamentally new antipathogen and anticancer therapies: ones that block the ability to evolve, instead of (or in addition to) traditional chemotherapies that kill cells or stop them from growing.

Insights from Space: Potential Role of Diet in the Spatial Organization of Chromosomes (first author: Justin Sullivan)
Excerpt from the conclusion:

…rapid and coordinated functional changes occur within cells in response to environmental factors that affect the epigenome (e.g., the nuclear receptor super-family mediated effects of glucocorticoids, thryroid hormones, vitamins A and D, polyunsaturated fatty acids on nuclear structure and function) [3]. Yet the question remains: How feasible is it to test this hypothesis and its significance in nutritional studies? In our opinion, 4C and ChIA-PET currently represent the most powerful and readily applicable proximity ligation technologies for the study of the effects of known factors (e.g., hormone receptors) in the coordination of nutrient responsive changes in genome structure and function.

My comment: We discussed what was know about spatial organization of chromosomes in our 1996 Hormones and Behavior review section on molecular epigenetics.

The Genome, positioning, timings. There are major structural differences between the X and Y chromosomes; e.g., centromeric aiphoid repeats sequences and distribution of heterochromatin (Graves, 1995; Wolfe et al., 1985). These structural differences correlate with sexually dimorphic chromosomal positioning within the nucleus and with male/female differences in replication timing of the active X, the inactive X, and the Y chromosomes, e.g., Boggs and Chinault (1994), Clemson and Lawrence (1996); Hansen, Canfield, and Gartler (1995). Increasingly the structure and timings within the nucleus are realized as contributing to gene expression regulation (Manders, Stap, Strackee, van Driel, and Aten, 1996; Stein, Stein, Lian, van Wijnen, and Montecino, 1996).

See also: Genetic tests reveal need for vitamins (
To my knowledge, the only published work to link my model of nutrient-dependent insect polyphenisms,  RNA-directed DNA methylation and RNA-mediated amino acid substitutions to healthy development and to pathology via the spacial organization of chromosomes comes from Anna Di Cosmo’s group. For example, see: Role of olfaction in Octopus vulgaris reproduction

The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000).

If the editors and authors whose works are published in the “Special Issue Nutritional Epigenetics” had mentioned Elekonich and Robinson (2000): Organizational and activational effects of hormones on insect behavior, in the context of the other works I cited and they cited, others could have linked the citation to our 1996 review to the life history transitions of the honeybee model organism in Elekonich and Roberts (2005) Honey bees as a model for understanding mechanisms of life history transitions.
This would lead them to Kohl (2013) Nutrient-dependent/pheromone-controlled adaptive evolution: a model and also to what is known about the role of GnRH, which was detailed in Feedback loops link odor and pheromone signaling with reproduction.
Instead, the “Special Issue Nutritional Epigenetics” leads nowhere. It fails to integrate what is already known about nutrient-dependent microRNAs and the RNA-mediated cell type differentiation that links GnRH to differences in cell types of mammals via differences in morphology and behavior in all vertebrates and a model of RNA-mediated cell type differentiation that links all cell type differentiation in all individuals of all genera. The special issue is an example of how those who cannot integrate what is known, ignore the obvious need for a model and continue to present findings that support academia, but do not lead to scientific progress.
See for comparison: Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing.
Others continue to link nutritional epigenetics to pharmacogenomics via the pathway I have detailed in a series of published works since book publication in 1995.
From Kohl (2012)
The gene, cell, tissue, organ, organ-system pathway is a neuroscientifically established link between sensory input and behavior. Marts and Resnick (2007) stress the importance of this pathway in the context of a systems biology approach to pharmacogenomics. Naftolin (1981) stressed its importance to the understanding of sex differences. This pathway is sensitive to conditioning. Sensory input from an organism’s environment activates and reactivates the pathway and causes changes in hormone secretion that condition hormone-driven behavior.

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