Does the Epigenome Hold Clues to Leptin-associated Hypertension in Obesity?

Lingappan, Krithika

doi:10.1165/rcmb.2021-0199ed

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…Our results confirm the previous reports highlighting possible effects of environmental conditions and lifestyle choices as key stressful factors that progressively induce tissue-specific adaptation processes (allostasis processes) to maintain homeostasis. This occurs through the activation of several signaling and metabolic pathways, as well as through the modulation of the epigenetic/epigenomic clock [ 79 , 80 , 81 , 82 , 83 , 84 ]. These cumulative “stress” factors will over time exert an immunometabolic overload and induce homeostasis disturbances that favor the onset and/or the progression of chronic diseases ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…These discrepancies could also be due to the fact that BMI is not a very accurate parameter to predict obesity status [ 70 ]. Other factors such as leptin circulating levels, the gene expression pattern of both LEP and its receptor LEPR, the epigenetic events (DNA CpG islands methylation events as shown in this study) affecting the LEP gene, the LEPR (Ob-R) polymorphism (including the long active isoform Ob-Rb, the short LEPR isoforms (Ob-Ra, Ob-Rc, Ob-Rd), and the soluble LEPR isoform (Ob-Re)) should be considered to better understand the downstream LEP signal transduction pathways to define more accurately both the LEP prognostic and predictive value, and to refine the cohort of cancer patients that will have better outcomes [ 70 , 84 , 88 ]. The involvement of several genes and multiple molecular/signalling oncogenic pathways (including growth factors, Notch, and pro-inflammatory signalling) events along with LEP gene promoter methylation, protein expression, and the obesity-related metabolic events highlight the magnitude and complexity of LEP molecular functions in both health or disease as discussed earlier ( Figure 4 ) [ 49 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

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Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Assidi

Yahya

Al-Zahrani

et al. 2021

IJMS

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Ovarian cancer (OC) is the deadliest among all gynecological cancers. Epidemiological studies showed that obesity might influence many cancers including OC. One of the key factors that may link obesity and OC is leptin (LEP), known as an adipokine with pleiotropic effects on body homeostasis. This study aims to investigate the expression pattern of LEP, assess the methylation profiles of LEP and their associations with clinicopathological features including survival outcomes of OC patients. The protein expression of LEP was evaluated in 208 samples using both tissue microarray and immunohistochemistry techniques. The methylation profiles of LEP were measured in 63 formalin-fixed, paraffin-embedded tumor tissues by quantitative polymerase chain reaction using a MethyLight assay. Our results showed a significant association of LEP protein overexpression with several clinicopathological variables, mainly tumor subtype, LVI, age of menarche, tumor size and stage (p < 0.04). Kaplan–Meier analysis (using low expression versus high expression as a discriminator) indicated that LEP protein overexpression is a powerful positive prognosticator of both OC recurrence (DFS) and disease-specific survival (DSS) in our OC cohort (log-rank p = 0.01 and p = 0.002, respectively). This implies that patients with high LEP expression profiles live longer with less recurrence rates. Methylation analysis results demonstrated a clear association between no/low LEP protein expression pattern (38%) and LEP promoter CpG island hypermethylation (43%). Results of this study suggest that LEP is a powerful prognosticator of OC recurrence and DSS. LEP expression in OC seems to be regulated by its promoter hypermethylation through gene partial/total silencing. Further multi-institutional studies using larger cohorts are required to demystify the intricate molecular functions of this leptin-driven effects in OC pathophysiology and to accurately assess its theranostic potential and validate its prognostic/predictive power in OC onset, progression towards more effective and personalized management of OC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Assidi

Yahya

Al-Zahrani

et al. 2021

IJMS

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Controversial culprit of leptin in obesity hypertension: clues from a case-control study with Chinese newly diagnosed adult early-onset obesity hypertensives

Leng

Zhang

et al. 2022

Clinical and Experimental Hypertension

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Reevaluating Adiponectin’s impact on obesity hypertension: a Chinese case-control study

Wu,

Lu,

Leng

et al. 2024

BMC Cardiovasc Disord

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Background Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study. Methods A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. Results Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model. Conclusions Our study reveals that adiponectin’s role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the “adiponectin paradox”.

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Does the Epigenome Hold Clues to Leptin-associated Hypertension in Obesity?

Cited by 3 publications

References 14 publications

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Controversial culprit of leptin in obesity hypertension: clues from a case-control study with Chinese newly diagnosed adult early-onset obesity hypertensives

Reevaluating Adiponectin’s impact on obesity hypertension: a Chinese case-control study

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