The big complicating factor here is epigenetics, for which the Cleveland Clinic offers an elegant definition:
Epigenetics is the study of how our environment influences our genes by changing the chemicals attached to them. What we eat, our physical activity level, access to resources and more affect those chemicals, in turn shaping our health.
As it turns out, a lot of aspects of the human condition which were assumed to be hardwired, or totally determined by genes, are actually malleable, whether or not we currently understand the processes behind how all of this works.
So, on one level, the genes we inherit say “This is how it’s gonna be.” Then, the science of epigenetics comes along and says, “Except when it isn’t, and boy oh boy, do we ever still have a lot to learn about that!”
Today we consult the National Library of Medicine for an overview of contemporary knowledge and thinking about the relationship between obesity and genetics. The authors are Ekta Tirthani, Mina S. Said (both of Rochester General Hospital), and Anis Rehman (Northern Virginia Medical Center). There is, to use a non-technical and totally accurate phrase, a lot going on. The only factor that is a bedrock certainty is maternal health — and just to deal with that one aspect requires “a team of obstetricians, pediatricians, nutritionists, geneticists, psychologists.”
Diagnosis of genetic and/or epigenetic origins of obesity
Here is an abbreviated version, just the highlights, of the authors’ explanation of how to figure this out in any individual case, and it is no walk in the park:
Endocrine causes of obesity […] must be ruled out early with history, physical examination, and lab work. Syndromic obesity can sometimes be distinctly diagnosed based on the presence of physical features… After basic lab work is done […] physicians can check leptin, insulin, and proinsulin levels. If all the above blood work is negative genetic testing can be carried out.
This is where it gets really complicated, involving arcane lab work that is only available in a few advanced facilities, and costs a bundle because of the expensive equipment required, along with the detailed high-level knowledge in obscure fields. But wait, there is more.
Research is necessary into the individual’s family history and personal history, as well as several other areas of life: psychosocial environment, habitual dietary practices, everyday activities, purposeful exercise, medications, and the subject’s (or patient’s) unique pattern of weight gain and loss thus far.
Two drugs are FDA-approved for treating genetically caused obesity, while several others (like the semaglutide and liraglutide we hear so much about) are working hard to prove their worth in that arena.
Even when obesity is passed down through the genes, various interventions can make a difference. The implementation of many different interventions can eliminate, at least partially, the validity of “I can’t help myself, it’s genetic” as a rationale. Sometimes the problem is clearly not genetic.
Or is it? An entire branch of philosophy could be based on arguing that, ultimately, everything and anything in the realm of human behavior might be genetic in origin. The manuscript describes these areas in much greater detail. The interventions that are mentioned and their mechanisms include:
— Bariatric surgery can cause changes in adipocyte-derived exosomal micro-RNA and cause epigenetic changes in differential methylated regions…
— Regular exercise can cause widespread changes in DNA methylation… For patients who maintain their weight loss, the DNA methylation profiles resemble lean individuals…
— Fasting can cause changes in DNA methylation of genes…
— The use of probiotics, prebiotics, and fecal transplant can restore gut flora and cause positive epigenetic modifications…
One principle is impossible to overemphasize: Obesity is multifactorial. In this area of human health, genetic factors do not equal the Implacable Hand of Fate or any such fatalistic notion. There is, in other words, plenty of room for improvement.
(To be continued…)
Your responses and feedback are welcome!
Source: “Epigenetics,” ClevelandClinic.org, undated
Source: “Genetics and Obesity,” Genetics and Obesity, nih.gov, 07/31/23
Image by Kevin Simmons/Attribution 2.0 Generic/
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