Oversize Bodies and Itty-Bitty Genes, Continued

Nature is able to circumvent expectations and even reason, and science should not be blamed for underestimating that possibility, because cause and effect are not always blatantly obvious. Previously we mentioned a Netherlands study showing that “men who were still in the womb when their mothers experienced malnutrition tended to have children with a tendency to become overweight adults.”

In other words, the effect carries on into the third generation. Such weirdness can be explained by accepting that genes do not interact only with one another, but with such environmental factors as temperature, acidity, and nutrients, as well as elements that are not yet recognized.

War, separation from loved ones, and many other types of stress can cause a person’s physiology to change in ways that are heritable, while their genetics remain unchanged. In Greek, “epi” means over, on top of, or in addition to. In this case, it signifies that cell function can change in a way that will be stable and is heritable, while the DNA sequence remains unchanged. This happens because of the world around us, when “our environment influences our genes by changing the chemicals attached to them,” and sometimes because of choices we make such as “what we eat, our physical activity level, access to resources and more.”

All this implies that, since some characteristics are changeable, we are better off figuring out how to play a deliberate and purposeful role, rather than heedlessly accept whatever random experiments some corporation wants to perform on us, and especially in preference to letting things happen to us through our own neglect. Sadly, depending on one’s gender, age, parental status, state of health, and many other factors, the average grownup does not like to think too much about this whole subject.

What moms do matters

Many women like to learn about the best veggies to eat while pregnant, but very few would enjoy an in-depth analysis of how their habits during and even before pregnancy quite possibly messed up the lives of their existing children. Guilt alone is oppressive enough, but guilt for something that can never be taken back or corrected is a potentially catastrophic burden. For a mother in that position, blame can come from three directions: herself, the child, and the biological father. If the child is born with, for instance, a problem that her smoking habit probably caused, there is the recipe for a lifetime of misery.

With maternal smoking alone, possible consequences include miscarriage, premature birth, stillbirth, placental abruption, placenta previa, low birth weight, and increased risk of defects like cleft lip and cleft palate. The fetus might not get enough oxygen, and lung problems are a possibility. There could be abnormal bleeding during pregnancy or delivery. Even after a seemingly successful delivery, the chance of Sudden Infant Death Syndrome is increased.

It transcends the personal

There is another problem. The entire health insurance industry is already a nightmare for patients and families to deal with. When a baby shows up with medical problems, a thorough study of all the epigenetic possibilities could cause a horrific situation. If detectives were to compile cases against mothers who, for instance, smoked cigarettes while pregnant, this could lead to, among other consequences, court battles capable of consuming fortunes and lifetimes.

What about childhood obesity, and a mother’s liability if her child turns out to be dangerously obese? A report titled “The Effect of Maternal Overweight and Obesity Pre-Pregnancy and During Childhood in the Development of Obesity in Children and Adolescents: A Systematic Literature Review” examined 11 studies on the subject. Some looked at maternal overweight or obesity before conception, and found “consistent positive associations with childhood obesity,” while others reported “positive associations between childhood obesity and maternal overweight/obesity during childhood.” The paper goes on to say,

This review has confirmed the multifactorial etiology of childhood obesity, indicating that maternal overweight and obesity has an important role in the development of childhood obesity, regardless of its occurrence (i.e., before the child’s conception or during childhood).

Still, the book we discussed, Genetics and Obesity, named factors that can overrule the gene pool and cause positive deviations. Bariatric surgery affects micro-RNA and can cause epigenetic changes. A staunchly maintained exercise schedule “can cause widespread changes in DNA methylation.” So can fasting.

And if positive epigenetic modification is what we want, it can be obtained with prebiotics and probiotics and even with fecal transplants to build up and perk up the gut microbiome. In other words, a conscientious prospective mother can plan ahead, and quit smoking or lose weight or otherwise “clean up her act” and provide a safe and welcoming womb for a fetus to inhabit.

(To be continued…)

Your responses and feedback are welcome!

Source: “Epigenetics,” ClevelandClinic.org, undated
Source: “Genetics and Obesity,” NIH.gov, 07/31/23
Source: “Smoking During Pregnancy,” WebMD.com, 10/04/24
Source: “The Effect of Maternal Overweight and Obesity Pre-Pregnancy and During Childhood in the Development of Obesity in Children and Adolescents: A Systematic Literature Review,” NIH.gov, 12/02/22
Image by The 5th Ape/Attribution 2.0 Generic

Oversize Bodies and Itty-Bitty Genes

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/

A “Strong” Study Looks at Pediatric Obesity Treatment

Children who respond positively to pediatric obesity treatment show significantly lower risks of health problems and early death in young adulthood, according to a study published on January 21 in JAMA Pediatrics.

The gist of the study

Led by Resthie R. Putri, Ph.D., and a team from the Karolinska Institutet in Stockholm, Sweden, the researchers analyzed data from 6,713 children and adolescents with obesity, drawn from Sweden’s Childhood Obesity Treatment Register (BORIS) and compared them to general population data. The study used baseline information collected between 1996 and 2019 and analyzed outcomes in 2023.

Study’s results

The study tracked health outcomes for young adults, ages 18-30, from 2005 to 2020. The participants included children aged 6-17 who had received at least one year of obesity treatment. These individuals were compared to a group from the general population matched for sex, birth year, and geographic location.

The research team categorized the participants’ responses to obesity treatment based on changes in their body mass index (BMI) standard deviation scores. These categories included poor, intermediate, good, or remission of obesity. Health outcomes in young adulthood that were assessed included type 2 diabetes, dyslipidemia, hypertension, depression or anxiety, and the need for bariatric surgery.

The findings showed that compared to a poor treatment response, those who achieved obesity remission or had a good treatment response were at much lower risk for early death. Additionally, a good response was linked to a lower likelihood of developing type 2 diabetes, dyslipidemia, and requiring bariatric surgery. Only the remission group showed a reduced risk for hypertension. However, treatment response did not appear to influence the risk of depression or anxiety, a noteworthy observation as it suggests that these mental health conditions need to be addressed separately from obesity.

The study’s large sample size and Sweden’s universal healthcare system, which facilitated continuous data tracking, were key strengths. The authors noted that the results may not be applicable to other countries, as the study’s findings are based on Swedish data.

The commentary

One of the study’s authors, Emilia Hagman, who is a principal researcher at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, commented:

The results are very good news. Whether or not the treatment of obesity in childhood has long-term health benefits has been debated, since weight-loss is hard to maintain… This emphasizes the importance of providing early treatment, as we know that timely intervention increases the likelihood of success and helps mitigate the long-term health risks associated with obesity.

In an accompanying commentary, Leonard H. Epstein, Ph.D., and colleagues praised the study for its robust design and the insights it offers into how much weight change is needed for significant health improvements, which could inform future treatment guidelines. However, they pointed out that the study didn’t specify the types or intensity of treatment provided to the children, which makes it difficult to compare with U.S. guidelines from the American Academy of Pediatrics (AAP).

The commentary also highlighted a key finding: Younger children (ages 6-11) had a higher rate of achieving good responses or remission compared to adolescents (ages 12-17). This suggests that earlier intervention in childhood may lead to better outcomes, emphasizing the importance of starting obesity treatment early rather than waiting to see if the child will “outgrow” the condition.

The bottom line

The study also found no strong connection between obesity treatment response and anxiety or depression, thus suggesting that these conditions should be treated independently of obesity. The study provides important evidence on how pediatric obesity treatment affects long-term health, including risks for cardiometabolic diseases, the need for bariatric surgery, and even mortality. This information is vital for refining clinical guidelines and improving obesity treatment strategies.

Your responses and feedback are welcome!

Source: “Successful Pediatric Obesity Treatment Linked With Long-Term Health,” Medscape, 1/22/25
Source: “Effect of Pediatric Obesity Treatment on Long-Term Health,” JAMA Network, 1/21/25
Source: “Weight-loss treatment for children with obesity has lasting effects, finds study,” MedicalXPress, 1/21/25
Image by Ketut Subiyanto/Pexels