Everything You Know About Thrifty Genes Is Wrong — 6

Very recently (October 2022) a paper was published with the daunting title, “The PPARGC1A Is the Gene Responsible for Thrifty Metabolism Related Metabolic Diseases: A Scoping Review.” It contains intriguing information for those who are interested in this sort of thing.

To verify its credentials, a thrifty gene can contribute to the regulation of energy balance, or it can work with metabolism or other physiological functions. A meta-study revealed that despite some inconsistent results, it appears that PPARGC1A Gly482Ser is the gene responsible for thrifty metabolism in the earth’s Pacific population. The paper states,

Positive selection of gene alleles associated with specific traits, such as obesity as a predisposing factor for non-communicable diseases, supports the thrifty gene theory hypothesis in terms of genetic susceptibility.

Differences in the prevalence of metabolic diseases in the population resulted from the frequency of polymorphisms and different risk alleles between populations.

The paper’s introduction provides several provocative statements:

The thrifty gene hypothesis can be understood in two forms: thrifty early and thrifty late. The thrifty early form corresponds more closely to Neel’s perspective, whereas the thrifty late form is the more common view among geneticists.

Genetic variations in genes related to metabolic diseases, especially diabetes mellitus, are considered to be candidates for thrifty genes in the population.

The brain runs on glucose, and in this worldview, the brain’s survival is a top priority. To get its fix, the brain has to make the body eat, and hold onto stored energy. In the past, a purpose was served. But nowadays, all that bogus energy, generated from ingredients with varying degrees of toxicity, is widely available and widely consumed. The authors say, “[I]ncreasing adiposity can induce a state of persistent low-grade inflammation and hence activate the insulin resistance pathways.” There’s more:

Diabetes as a multifactorial disease is thought to be a description of the failure of adaptation of gene alleles to current environmental conditions compared to previous conditions, thus, a wide variety of metabolic syndrome manifestations are associated with the response to these changes.

Adaptability is an awesome trait, but it can be either beneficial or detrimental. An adaptation that sticks around too long might find itself superseded and outmoded. An adaptation that benefits one organ or system at the expense of others is not the best answer. When too much glucose comes in and hangs around for too long, it would seem that further adaptation is called for. Part of the brain needs to tell the other part to slow its roll.

Your responses and feedback are welcome!

Source: “The PPARGC1A Is the Gene Responsible for Thrifty Metabolism Related Metabolic Diseases: A Scoping Review,” NIH.gov, 10/13/22
Image by Aloizio Mercadante Oliva/CC BY-SA 2.0

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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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