Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics

Motawi, Tarek K.; Shaker, Olfat G.; Ismail, Magda M. F.; Sayed, Noha H.

doi:10.1038/s41598-017-11180-6

Cited by 66 publications

(53 citation statements)

References 63 publications

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“…This suggests that miR-130a sEV content may predict adipose tissue perturbation, and thereby may be considered a specific signature of adipose tissue dysfunction in obese subjects. Finally, a significant negative correlation between PPARγ and circulating miR-130 level was reported in obese patients with colorectal cancer 59 . Therefore, to exploit miR-130 sEV content as a potential biomarker of colorectal cancer susceptibility in obese patients should be a further future challenge.…”

Section: Discussionmentioning

confidence: 84%

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Cavallari

Figliolini

Tapparo

et al. 2020

Sci Rep

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Serum-derived extracellular vesicles (sEV) from healthy donors display in-vivo pro-angiogenic properties. To identify patients that may benefit from autologous sEV administration for pro-angiogenic purposes, sEV angiogenic capability has been evaluated in type 2 diabetic (T2DM) subjects (D), in obese individuals with (OD) and without (O) T2DM, and in subjects with ischemic disease (IC) (9 patients/ group). sEV display different angiogenic properties in such cluster of individuals. miRNomic profile and tGfβ content in sEV were evaluated. We found that miR-130a and TGFβ content correlates with sEV in-vitro and in-vivo angiogenic properties, particularly in T2DM patients. Ingenuity Pathway Analysis (IPA) identified a number of genes as among the most significant miR-130a interactors. Gain-of-function experiments recognized homeoboxA5 (HOXA5) as a miR-130a specific target. Finally, ROC curve analyses revealed that sEV ineffectiveness could be predicted (Likelihood Ratio+ (LH+) = 3.3 IC 95% from 2.6 to 3.9) by comparing miR-130a and TGFβ content 'in Series'. We demonstrate that sEV from high cardiovascular risk patients have different angiogenic properties and that miR-130a and TGFβ sEV content predicts 'true ineffective sEVs'. These results provide the rationale for the use of these assays to identify patients that may benefit from autologous sEV administration to boost the angiogenetic process. Cardiovascular complications are relevant causes of morbidity and mortality in patients with diabetes and obesity 1. Recent evidence suggests that extracellular vesicles (EVs) may act as mediators of many pathophysiological processes 2-4. EVs are small vesicles that are released from different cell types under normal and pathological conditions 5,6. Increased levels of circulating EVs have been associated with vascular impairment and hypercoagulability, particularly in patients with diabetes and acute coronary syndrome, suggesting that they play a role in driving cardiovascular diseases 7,8. Moreover, increased levels of circulating EVs, mainly from platelets and endothelial cells, has been proposed as a hallmark of cell dysfunction 9. It has been extensively reported that EVs act as biological active vectors, and participate in the exchange of information between circulating and resident cells, including endothelial cells 2,10. It has also been proposed that platelet-derived EVs play a role in the pathogenesis of atherosclerosis 11. EVs act as biological intermediaries, and mainly do so by delivering proteins, active lipids and extracellular RNAs 12. However, the most frequently studied EV-mediated biological processes rely on microRNA (miRNA) transfer. miRNAs are a class of small noncoding RNAs post-transcriptionally regulating gene expression 13. miR-NAs are present in serum/plasma and it has been proposed that their distinctive expression patterns serve as disease fingerprints in many clinical settings 14. Moreover, it has been shown that activated platelets can transfer

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Section: Discussionmentioning

confidence: 84%

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Cavallari

Figliolini

Tapparo

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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“…Accumulating evidence highlighted that besides these unhealthy lifestyles and environmental factors, some additional inherited susceptibility factors may be associated with the development of CRC. As CRC is associated with obesity and Waist-to-Hip Ratio (WHR) (8–10), the peroxisome proliferator-activated receptor gamma ( PPARG ), PPARG co-activator 1 ( PPARGC1 ) family (e.g., PPARGC1A and PPARGC1B ) may be strong candidate genes predisposing to CRC (11).…”

Section: Introductionmentioning

confidence: 99%

PPARG rs3856806 C>T Polymorphism Increased the Risk of Colorectal Cancer: A Case-Control Study in Eastern Chinese Han Population

et al. 2019

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Purpose: Functional variants in the peroxisome proliferator-activated receptor gamma ( PPARG ) and PPARG co-activator 1 ( PPARGC1 ) family (e.g., PPARGC1A and PPARGC1B ) genes were predicted to confer susceptibility to colorectal cancer (CRC). The aim of the present study was to explore the relationship between PPARG, PPARGC1A, PPARGC1B polymorphism and the risk of CRC. Patients and methods: We conducted a case-control study with 1,003 CRC cases and 1,303 controls. We selected the PPARG rs3856806 C>T, PPARGC1A rs2970847 C>T, rs8192678 C>T, rs3736265 G>A and PPARGC1B rs7732671 G>C and rs17572019 G>A SNPs to assess the relationship between PPARG, PPARGC1A, PPARGC1B their variants and risk of CRC. Results: We found that the PPARG rs3856806 C>T polymorphism increased the risk of CRC (TT vs. CC: adjusted OR, 1.59, 95% CI 1.08–2.35, P = 0.020; TT/CT vs. CC: adjusted OR, 1.26; 95% CI 1.06–1.49; P = 0.009 and TT vs. CC/CT: adjusted OR, 1.54; 95% CI 1.05–2.26; P = 0.028), even after a Bonferroni correction test. The stratified analysis revealed that the PPARG rs3856806 C>T polymorphism also increased the risk of CRC, especially in male, ≥61 years old, never smoking, never drinking, BMI ≥ 24 kg/m 2 , colon cancer and rectum cancer subgroups. Conclusion: Our findings highlight that the PPARG rs3856806 C>T polymorphism may increase the risk of CRC. In the future larger sample size case-control studies with a detailed functional assessment are needed to further determine the relationship of the PPARG rs3856806 C>T polymorphism with CRC risk.

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“…The peroxisome proliferator‐activated receptor gamma gene ( PPARG ) is alternatively spliced to produce peroxisome proliferator‐activated receptor gamma 1 and 2 (PPARγ1 and PPARγ2), which are nuclear receptors involved in adipocyte differentiation, inflammation, and lipogenic pathways . In adults with obesity, evidence shows a decline in both activity and amount of PPARγ, which may be related to cancer development . In accordance with this data, Volberg et al reported that the methylation of some CpGs in the PPARG promoter, gene body, and 5′‐untranslated region (UTR) in the umbilical cord and blood displayed an inverse association with birthweight and with the 9‐year BMI z‐score .…”

Section: Genes and Pathways Studiedmentioning

confidence: 83%

An overview about DNA methylation in childhood obesity: Characteristics of the studies and main findings

Lima

Gomes

Moreira

2019

J of Cellular Biochemistry

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Childhood obesity is a global burden affecting millions of children worldwide. It is well-known that the adiposity profile in children is critical for future occurrence of diseases. As a multifactorial disease, obesity is associated with genetic and environmental factors. Epigenetic mechanisms link the plethora of environmental clues to a given phenotype. DNA methylation is the most studied epigenetic mark and its importance in several diseases was acknowledged. In childhood obesity, specifically, the studies show a consistent association between adiposity and methylation at the gene and genome-wide scales. The relationship between DNA methylation and childhood obesity has been proved strong for some genes and pathways. However, the studies are heterogeneous in their design, methodologies, and results. The aim of this review is to discuss this heterogeneity and point out some aspects that should be considered in future studies to clarify the role of DNA methylation in childhood obesity. K E Y W O R D Sadiposity, body mass, childhood obesity, DNA methylation, epigenetics

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Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics

Cited by 66 publications

References 63 publications

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

PPARG rs3856806 C>T Polymorphism Increased the Risk of Colorectal Cancer: A Case-Control Study in Eastern Chinese Han Population

An overview about DNA methylation in childhood obesity: Characteristics of the studies and main findings

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