Episode 130: Epigenetics in childhood obesity
Saakshi and Dr. Arreaza discuss some principles of epigenetics implicated in the development of obesity in children.
Written by Saakshi Dulani, MS3, Western University College of Osteopathic Medicine of the Pacific. Edited by Hector Arreaza, MD.
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This topic is constantly expanding, and I’m excited to talk about it. It is a fact that epigenetic changes play a role in the development of certain diseases such as Prader-Willi syndrome, Fragile X syndrome, and various cancers. It has been demonstrated that certain foods can alter gene expression in animals, for example.
What is epigenetics?
Epigenetics is the regulation of gene expression without a change in the base sequence of DNA. Epigenetics means “on top of” the genes. Genes can be turned “on” or “off” as a response to external influences.
Obesity and Epigenetics.
The link between genetics and obesity is complex, but it is known that epigenetics plays a significant role in childhood obesity. Surprisingly, exposure to environmental factors starts in the uterus.
Fetuses are exposed to intrauterine signals that increase their potential to develop obesity. Factors such as in-utero hyperglycemia, gestational diabetes mellitus, and early childhood diet and lifestyle practices can affect the development of the gut microbiome, modify gene expression through DNA methylation, and increase the risk of childhood obesity.
These gene expression changes can be passed on to future generations. DNA methylation is the addition of a methyl group to part of the DNA molecule. That methyl group acts as a “chemical cap,” which prevents gene expression. Another example of epigenetics is histone modification. Histones are proteins that are used by DNA as spools to wrap around pieces of information that are “not needed”. The reason why a scalp cell and a neuron are different is that the expression of certain genes is suppressed while other genes are expressed.
Factors that influence obesity.
Some factors that increase the risk of childhood obesity through epigenetic changes include neonatal intestinal microbiome, C-section delivery, maternal insulin resistance, exposure to antibiotics and other environmental toxins, early introduction of complementary foods, parental diets high in carbohydrates and low in fruits and vegetables, and poor sleep. There are many other factors, but we will discuss only a few of them.
Microbiome:
The microbiome is a whole new world that is being explored by many investigators. The gut microbiome refers to the diverse community of organisms, including bacteria, fungi, and viruses, that reside in the human intestine. The neonatal intestinal microbiome is established during the first two years of life and may be influenced by factors such as the method of delivery, maternal obesity, and the maternal gut microbiome.
Some bacteria worth mentioning are Bacteroides, Clostridium, and Staphylococcus. These gut bacteria are higher in pregnant women who have obesity, and they also have a low count of Bifidobacterium. Infants born to obese mothers have higher levels of bacteria associated with increased energy harvest compared to infants born to normal-weight mothers. The gut microbiome of infants delivered by C-section is different than infants delivered vaginally.
Link to antibiotics:
Early exposure to antibiotics is associated with the development of resistance in microorganisms. The intestinal microbiota exposed to antibiotics also shows reduced diversity. Antibiotics can decrease the number of mitochondria and impair their function, which is important in maintaining energy metabolism. Evidence suggests that some antibiotics can cause mutations in the mitochondrial genome, and they have a direct effect on the microbiome and influence metabolism. There is a strong association between early-life antibiotic exposure and childhood adiposity, with a strong dose-response relationship. A stronger association has been seen with exposure to broad-spectrum antibiotics and macrolides.
Maternal insulin resistance (IR):
Insulin resistance means that the mother needs levels of insulin that are higher than normal to stay normoglycemic. It means the insulin receptors are “exhausted” and do not respond to normal levels of insulin. Insulin does NOT cross the blood-placenta barrier, but glucose and other nutrients do. This causes the fetus to have an abundance of glucose that stimulates the secretion of high levels of insulin by the fetal pancreas to stay normoglycemic. The combination of insulin + glucose is the perfect combination for anabolism, adipocyte hyperplasia, and fetal growth. That explains why mothers with insulin resistance deliver larger babies (macrosomia).
Maternal insulin resistance is a predictor of infant weight gain and body fat in the first year of life. This is not influenced by the mother's BMI before pregnancy. Maternal insulin resistance causes alterations in gene regulation for lipids, amino acids, and inflammation, leading to long-term health implications for both the mother and future pregnancies.
C-section and obesity:
C-section delivery is a saving procedure for many obstetrical emergencies. C-sections have improved the survival of larger infants and their mothers. C-sections are more frequent among populations with obesity and sedentary lifestyles. This method of delivery is also strongly associated with childhood obesity. Among many other reasons, whenever a vaginal delivery is feasible, a vaginal delivery is preferred over a c-section.
In summary, we discussed 4 factors that may influence childhood obesity: the newborn microbiome, exposure to antibiotics, maternal insulin resistance, and C-sections. There are many other factors that we did not talk about, but the more we know about genetics, epigenetics, and metabolism, the closer we get to a better understanding of obesity.
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Conclusion: Now we conclude our episode number 130, “Epigenetics in childhood obesity.” Saakshi discussed with Dr. Arreaza that the in-utero environment can alter gene expression and increase the risk of obesity in children. Some factors, such as maternal insulin resistance and changes in gut microbiome, can be the cause of obesity in some children. This week we thank Hector Arreaza and Saakshi Dulani. Audio editing by Adrianne Silva.
Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week!
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Sources:
- Burdge GC, Hoile SP, Uller T, Thomas NA, Gluckman PD, Hanson MA, Lillycrop KA. Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition. PLoS One. 2011;6(11):e28282. doi: 10.1371/journal.pone.0028282. Epub 2011 Nov 30. PMID: 22140567; PMCID: PMC3227644. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227644/
- Rachael Rettner, Epigenetics: Definition & Examples, Live Science, published on June 24, 2013, available at: https://www.livescience.com/37703-epigenetics.html
- Mulligan CM, Friedman JE. Maternal modifiers of the infant gut microbiota: metabolic consequences. J Endocrinol. 2017;235: R1-R12.
- Aghaali, M. and S. S. Hashemi-Nazari (2019). “Association between early antibiotic exposure and risk of childhood weight gain and obesity: a systematic review and meta-analysis.” J Pediatr Endocrinol Metab 32(5): 439-445.
- Yuan C, Gaskins AJ, Blaine AI, et al. Association between cesarean birth and risk of obesity in offspring in childhood, adolescence, and early adulthood. JAMA Pediatr. 2016;170(11):e162385. doi: 10.1001/jamapediatrics.2016.2385.
- Royalty-free music used for this episode: “Gushito - Burn Flow." Downloaded on October 13, 2022, from https://www.videvo.net/
