Diving Into the Gene Pool

By 2017, most researchers had accepted that, when it comes to recognizing exactly what constitutes the developmental pathway to obesity, “multi-factorial” is the word of the century. One of the three major compartments is genetic risk, whose effects are fixed (although, the way things are going, that could conceivably change in the future.) Each susceptible gene is a factor in itself, and by then, 300 genes had been identified as susceptible to alteration in ways that could contribute to obesity.

The other two major areas, epigenetic and environmental variations, are “dynamic and modifiable,” which is a concise way of saying that they add thousands of potential additional factors. Senior Principal Investigator and Systems Biology lead at Singapore Institute for Clinical Sciences Neerja Karnani wrote,

Besides their individual effects, genetic, epigenetic and environmental factors can influence each other’s role, or work in an additive way in disease predisposition. Most studies in the past have primarily looked at the role of these factors independently, but rarely attempted a combined analysis.

Sure, prenatal factors had been identified, 11 of them, including maternal obesity and maternal smoking. Birthweight variations had been linked with seven gene loci prone to DNA methylation changes. Combined analysis of so many factors is of course only possible through the existence of computers to keep track of immense numbers of numbers.

But even with that help, it will be a long time before all the possible contributing factors are accounted for, and even longer before anyone figures out how the combined effects of environmental, genetic, and epigenetic conditions work together to form those developmental pathways. The key to the future is figuring out the combined contributions of vast numbers of variables.

A 2017 study title read, “Fat mass and obesity-associated gene (FTO) is associated to eating disorders susceptibility and moderates the expression of psychopathological traits.” The authors wrote about the many factors that contribute to eating disorders, including not only biology but psychology and the environment:

We propose a model of interactions between genetic vulnerability — represented by Fat Mass and Obesity-Associated (FTO) gene — and stable psychopathological traits, such as bodily disorders and emotion dysregulation for EDs patients.

Various studies found relationships with binge-eating disorder, anorexia nervosa, and bulimia nervosa. Still…

Notwithstanding the hypothetically relevant connection between EDs, satiety and appetite regulation, conflicting results have so far been reported about the possible associations between FTO and EDs.

Here is an interesting paragraph from the Discussion section:

FTO rs9939609 variant represents a putative risk factor for people with high disorder of bodily disorders to develop emotional eating. As extensively reported in the literature, emotional eating is a pathological behavior, which accounts for development of obesity and for several pathological eating behaviors such as binge eating.

These genes also mess around with dopamine, reward learning, behavioral responses, the neural processing of food images, emotional eating, memory, self-image, and the regulation of fat mass.

Your responses and feedback are welcome!

Source: “Obesity — The complex story of its birth,” BioMedCentral.com, 03/07/17
Source: “Fat mass and obesity-associated gene (FTO) is associated to eating disorders susceptibility and moderates the expression of psychopathological traits,” PLOS.org, 03/10/17
Image source: Visualhunt

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About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
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Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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