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Written Assignment Unit 7

This document discusses the role of epigenetic mechanisms in the development of obesity, highlighting how environmental factors and gene regulation contribute to this metabolic disorder. Key genes such as FTO, PPARG, and LEP are affected by epigenetic changes like DNA methylation and histone modifications, leading to disrupted metabolic pathways. The paper emphasizes the potential for therapeutic interventions targeting these epigenetic alterations to combat obesity and its related health issues.

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12 views5 pages

Written Assignment Unit 7

This document discusses the role of epigenetic mechanisms in the development of obesity, highlighting how environmental factors and gene regulation contribute to this metabolic disorder. Key genes such as FTO, PPARG, and LEP are affected by epigenetic changes like DNA methylation and histone modifications, leading to disrupted metabolic pathways. The paper emphasizes the potential for therapeutic interventions targeting these epigenetic alterations to combat obesity and its related health issues.

Uploaded by

williammathias599
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Epigenetic Mechanisms in Obesity

Written Assignment Unit 7


University of the People
CHEM 3212-01 - AY2025-T2 Biochemstry
Instructor: Emma Awuku-Sowah
27/12/2024.

Epigenetic Mechanisms in Obesity


Epigenetic Mechanisms in Obesity

Introduction

Metabolic disorders have seen an alarming rise in prevalence globally, affecting diverse
populations across all age groups. Obesity, a leading metabolic disorder, is not only a
significant public health concern but also a precursor to other metabolic diseases such as type
2 diabetes, cardiovascular diseases, and certain cancers. While genetic factors contribute
minimally to obesity susceptibility, emerging research highlights the profound role of
epigenetics in regulating metabolic pathways and increasing disease prevalence. This essay
explores obesity as a metabolic disorder with an epigenetic "cause," focusing on the aberrant
regulation of specific genes, the underlying epigenetic mechanisms, and how these alterations
disrupt metabolic pathways.

Background of Obesity

Obesity is characterized by excessive accumulation of adipose tissue resulting from an


imbalance between caloric intake and expenditure. Its etiology is multifactorial, involving
interactions among environmental factors, lifestyle, and genetic predispositions. According to
Lam et al. (2023), obesity’s impact extends beyond physical health to include economic and
psychosocial burdens. Despite significant advances in understanding obesity’s biological
underpinnings, genetic variations explain only a small proportion of obesity risk. Epigenetics
has emerged as a critical factor bridging environmental influences, such as diet and physical
activity, with gene expression changes that predispose individuals to obesity and related
metabolic disorders.

Epigenetic Regulation of Key Genes in Obesity

Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding


RNAs, have been implicated in the aberrant regulation of genes associated with obesity. One
of the most studied genes is FTO (fat mass and obesity-associated gene). Aberrant DNA
methylation in the promoter region of FTO is associated with increased expression,
contributing to elevated appetite and reduced energy expenditure (Ling & Rönn, 2019).
Another key gene is PPARG (peroxisome proliferator-activated receptor gamma), a
master regulator of adipogenesis. Hypermethylation of PPARG’s promoter region has been
Epigenetic Mechanisms in Obesity

linked to impaired adipocyte differentiation, which exacerbates metabolic imbalances in


obesity (Rosen et al., 2018).

Epigenetic Mechanisms Influencing Obesity

DNA methylation plays a pivotal role in regulating genes involved in energy homeostasis and
lipid metabolism. For instance, hypermethylation of the leptin gene (LEP), responsible for
appetite regulation, leads to leptin resistance, a hallmark of obesity (Van Dijk et al., 2015).
Histone modifications, such as acetylation and methylation, also modulate chromatin
structure and gene accessibility. Altered histone acetylation patterns in genes regulating
mitochondrial function have been observed in obese individuals, impairing oxidative
metabolism (Wu & Yin, 2022). Additionally, non-coding RNAs, particularly microRNAs
(miRNAs), contribute to post-transcriptional regulation. Dysregulated miRNAs, such as miR-
33, inhibit genes involved in fatty acid oxidation, further promoting lipid accumulation.

Pathway Disruption in Obesity

The epigenetic regulation of these genes alters critical metabolic pathways, leading to the
development and progression of obesity. For example, increased FTO expression enhances
ghrelin levels, a hormone that stimulates appetite, thereby disrupting energy balance.
Similarly, hypermethylation of PPARG impairs adipogenesis, leading to ectopic fat
deposition and insulin resistance (Yang et al., 2022). Disruption in leptin signaling due to
LEP hypermethylation contributes to unregulated food intake and weight gain. These
alterations collectively compromise metabolic flexibility, making it challenging for
individuals to adapt to changes in nutrient availability and energy demands.

Environmental Influences on Epigenetic Changes

Environmental factors, including diet, physical activity, and exposure to toxins, significantly
influence epigenetic modifications in obesity. High-fat and high-sugar diets have been shown
to induce DNA methylation changes in metabolic genes, perpetuating obesity-related
phenotypes (Rosen et al., 2018). Physical inactivity exacerbates histone acetylation patterns
Epigenetic Mechanisms in Obesity

associated with mitochondrial dysfunction, reducing energy expenditure. Interestingly, some


epigenetic changes are reversible, highlighting the potential for lifestyle interventions and
pharmacological therapies targeting epigenetic marks to mitigate obesity and its
complications (Ling & Rönn, 2019).

Therapeutic Implications and Future Directions

Understanding the epigenetic mechanisms underlying obesity opens new avenues for
therapeutic interventions. Epigenetic drugs, such as DNA methyltransferase inhibitors and
histone deacetylase inhibitors, have shown promise in preclinical studies. Moreover, lifestyle
interventions, including dietary modifications and exercise, can reverse certain epigenetic
marks, restoring normal metabolic function (Wu & Yin, 2022). Future research should focus
on identifying specific epigenetic biomarkers for obesity to enable personalized treatment
approaches and early interventions.

Conclusion

Obesity’s rising prevalence underscores the need to unravel its complex etiology beyond
genetic predispositions. Epigenetic mechanisms, including DNA methylation, histone
modifications, and non-coding RNAs, play a significant role in aberrantly regulating genes
such as FTO, PPARG, and LEP, disrupting metabolic pathways and predisposing individuals
to obesity. Environmental influences further exacerbate these epigenetic changes,
emphasizing the interplay between lifestyle and gene expression. Advances in epigenetic
research offer hope for developing targeted therapies and preventive strategies to combat
obesity and its associated metabolic disorders.
Epigenetic Mechanisms in Obesity

References

Lam, B. C. C., Lim, A. Y. L., Chan, S. L., Yum, M. P. S., Koh, N. S. Y., & Finkelstein, E. A.
(2023). The impact of obesity: a narrative review. Singapore Medical Journal, 64(3), 163–
171. https://doi.org/10.4103/singaporemedj.smj-2022-232

Ling, C., & Rönn, T. (2019). Epigenetics in human obesity and type 2 diabetes. Cell
Metabolism, 29(5), 1028–1044. https://doi.org/10.1016/j.cmet.2019.03.009

Rosen, E. D., Kaestner, K. H., Natarajan, R., Patti, M., Sallari, R., Sander, M., & Susztak, K.
(2018). Epigenetics and Epigenomics: Implications for diabetes and Obesity. Diabetes,
67(10), 1923–1931. https://doi.org/10.2337/db18-0537

Van Dijk, S. J., Tellam, R. L., Morrison, J. L., Muhlhausler, B. S., & Molloy, P. L. (2015).
Recent developments on the role of epigenetics in obesity and metabolic disease. Clinical
Epigenetics, 7(1). https://doi.org/10.1186/s13148-015-0101-5

Wu, F., & Yin, R. (2022). Recent progress in epigenetics of obesity. Diabetology &
Metabolic Syndrome, 14(1). https://doi.org/10.1186/s13098-022-00947-1

Yang, M., Liu, S., & Zhang, C. (2022). The related metabolic diseases and treatments of
obesity. Healthcare, 10(9), 1616. https://doi.org/10.3390/healthcare10091616

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