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Obesity: A Problem Greater Than Just High Blood Pressure

Obesity remains an epidemic in the US as well as worldwide. Little has been studied and understood about the epigenetic basis of obesity in adolescents. There has been found an association between the level of DNA methylation in obesity-related genes and BMI percentile. In the last decade, a novel mechanism of epigenetic regulation of gene expression has been studied. Although there is increased awareness of lifestyle and environmental factors associated with obesity, there remain major gaps that exist in understanding the contribution of epigenetics.

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Obesity has been attached to many other health issues. One of them is colorectal cancer (CRC) has been determined to be a risk because of the relationship being mediated by epigenetic regulation. The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC. The analysis revealed statistically significant differences at 299CpG sites and they were mostly characterized as changes toward CpG hypermethylation occurring in the obese group (BMI ˃25Kg/m²). Among these genes, novel genes were identified as epigenetically regulated in CRC depending on the adiposity (amount of fat or adipose tissue). This study identifies a potential epigenome mark of obesity-related CRC that could be useful for precision medicine in the management of this disease taking into account the amount of fat tissue as a relevant risk factor (Crujeras et al, 2019).

How serious is the number of obese people
According to the world health organization (WHO), obesity has reached proportions of a pandemic. Experts are also insisting that obesity should be classified as a chronic condition. There is a large body of evidence that points to the correlation between obesity and colorectal cancer. In addition, there is a strong relationship between up to 13 different types of cancer and obesity. Adipose tissue is transferred to cancer cells and used for energy production. Because of the rapid expansion of adipose cells creates an environment that encourages tumor growth. Two large scale studies have identified a large number of DNA methylation loci associated with BMI. Clearly, more evidence is needed in order to determine the role of epigenetic process in obesity but assessing the epigenome at the proper time and relevant tissues an important barrier for human studies. Recent studies, however, have shown there is a connection between alterations in DNA methylation and its interaction with adipose tissue. It seems that the process of becoming obese is the consequence instead of the cause of it. This study has identified a novel miRNA-based theragnostic tool to help cancer patients within the not too distant future (Ayers, Boughanem, & Marcus-Gonzalez, 2019).

Metabolic syndrome (MetS) has been considered to raise the risk of type 2 diabetes, cardiovascular disease, and cancer. Adipose tissue plays an important role in metabolic homeostasis and adipose tissue (AT) dysfunction has been found to have an active role in metabolic disorders. Epigenetic has emerged as an interesting landscape to evaluate the possibility of interconnection between AT and metabolic disease. DNA methylation is one of the epigenetic mechanisms present in the cell. This substance, in addition, to other epigenetic mechanisms could explain in part how metabolic syndrome occurs. The study has shown these patients with metabolic syndrome clearly have a metabolic deterioration with higher BMI, waist circumference, glucose, insulin, total cholesterol, and high blood pressure. Epigenetic marks can be changed under the developmental process, nutritional conditions, exercise or metabolic status. And although this study showed general stability in the DNA methylation of the adipose tissue there were some differences in specific genes found between the non-MetS group when compared to the MetS group (Castellano-Castillo et al, 2019b).

Current research
Adipose tissue is considered an important metabolic tissue, in charge of energy storage as well as being able to act in systemic homeostasis and inflammation. Epigenetics involves a series of factors important for gene regulation or for chromatin structures. Mostly this presents as DNA methylation and histone-tail modification which can be modified by environmental conditions (lifestyle, nutrition, smoking). This study took human adipose tissue secured during various surgeries and once collected it was immediately frozen to ­80°C. Then it underwent a specific process in order to prepare it for study. Obesity and its related disorders have become one of the greatest health problems in developed countries. Adipose plays an important role of active tissue that can produce a multitude of signaling molecules that affect the functions of the whole body. In addition, it plays a role in metabolic homeostasis. Obesity is accompanied by an increase in fat mass proportion, adipose tissue dysfunction, and increased inflammation. The study produced statistical differences observed between groups for BMI, waist circumference, and serum levels of glucose. It was found also that S-Adenosy methionine (SAM), a methyl-group molecular donor for a wide range of reactions. Also, the study showed that SAM levels increase with the BMI and the increase with adiposity (excessive build-up of lipids in a site or organ). A reduction of fatty acid oxidation and glucose incorporation is seen in insulin resistance states (Castellano-Castillo et al, 2019a).

Obesity is considered one of the most important metabolic diseases of this century. It is linked to several co-morbidities including colorectal cancer. And despite the numerous epidemiological evidence connecting obesity to higher cancer risk and mortality, mechanisms involved are not fully known. Current evidence suggests there is a connection between visceral abdominal fat and obesity-associated co-morbidity and mortality. Environmental and lifestyle factors may influence epigenetic mechanisms like DNA methylation. In addition, there is evidence from previous studies that vitamin D level and excess body weight are related to CRC. This study was conducted on one group with a known diagnosis of CRC and one group is known not to have it. This study was the first time investigation into the LINE-1 methylation levels in visceral abdominal fat from cancer patients in relation to the control group. However, they did find a strong connection between LINE-1 methylation in visceral abdominal fat and vitamin D in the CRC group; vitamin D was the main variable influence on global DNA methylation in the study. Evidence exists that says dietary components may influence the inflammatory process and the risk of developing CRC (Castellano-Castillo et al, 2019c).

Conclusion
Since reprogramming energy metabolism is considered a new hallmark of cancer tumor metabolism is again in the spotlight of cancer research. Metabolic features of the cells are being studied in depth in order to find relationships between metabolisms within the microenvironment of tumor cells. It has been witnessed that highly proliferative cancer cells have a strong attraction to lipids, increasing the lipogenesis and cholesterol synthesis. A substance known as IL-6 is secreted from the tumor and can stimulate the excretion sugar (glucose) from the liver to help feed the tumor. There are two major types of T cells: CD4⁺ and CD8⁺ that are classified into different subtypes. CD8⁺ T cells often differentiate into cytotoxic T cells known to induce apoptosis or genetically directed cell death that gets halted by cell mutation leading to uncontrolled cell growth like tumor production. This study explored the metabolism within the tumor microenvironment and its effect on tumor growth and progression. Future studies should not just focus on the metabolism of the tumor microenvironment but the changes in the metabolism of the whole organism (Ocaña et al, 2019).

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Work Cited
Ayers, D., Boughanem, H. & Marcis-Gonzalez. (2019). Epigenetic influences in the obesity/colorectal cancer axis: A novel theragnostic avenue. Journal of oncology.

Castellano-Castillo,D. et al. (2019a). Human adipose tissue H3K4me3 histone mark in adipogenic, lipid metabolism and inflammatory genes in positively associated with BMI and HOMA-IR. PLoS ONE,14(4).

Castellano-Castillo, D. et al. (2019b). Altered adipose tissue DNA methylation status in metabolic syndrome: Relationships between global DNA methylation and specific methylation at adipogenic, Lipid metabolism and inflammatory candidate genes and metabolic variables. Journal of Clinical Medicine, 8(1).

Castellano-Castillo, D. et al. (2019c). Association between serum 25-hydroxyvitamin D and global DNA methylation in visceral adipose tissue from colorectal cancer patients. BMC Cancer.

Crujeiras, A.B. et al. (2019). Identification of an episignature of human colorectal cancer associated with obesity by genome-wide DNA methylation analysis. International Journal of Obesity, 43.

He, F. et al. (2019). Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents. Scientific Reports,9(2079).

Ocaña, M.C. et al. (2019). Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target. Medical Research Review.

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