Transcriptional Alterations of ET-1 Axis and DNA Damage in Lung Tissue of a Rat Obesity Model

Ry, Silvia Del; Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela; Scarpato, Roberto

doi:10.1089/dna.2014.2705

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…Obesity, a significant public health issue, is linked to an increased prevalence of chronic diseases. [1][2][3] According to the World Health Organization, the rate of obesity has tripled since 1975, and an estimated 50% of adults over the age of 18 are overweight/obese (WHO, 2018). 4 Despite significant efforts in China to eradicate severe obesity, the prevalence of obesity continues to rise, particularly in rural areas with few resources.…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population

Huan,

Wang,

Song

et al. 2023

Andrology

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BackgroundFew studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men.Materials and methodsThis cross‐sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography–tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity.ResultsAfter adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high‐sensitivity C‐reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high‐sensitivity C‐reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist‐to‐hip ratio), 12.92% (defined by waist‐to‐height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity.ConclusionInflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases.

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Section: Introductionmentioning

confidence: 99%

“…Obesity, a significant public health issue, is linked to an increased prevalence of chronic diseases 1–3 . According to the World Health Organization, the rate of obesity has tripled since 1975, and an estimated 50% of adults over the age of 18 are overweight/obese (WHO, 2018) 4 .…”

Section: Introductionmentioning

confidence: 99%

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population

Huan,

Wang,

Song

et al. 2023

Andrology

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“…The plasma ET-1 concentration level in diabetic patients is positively correlated with microangiopathy. ET-1 is also significantly increased in obesity [ 18 , 19 ]. Chronic inflammation causes obesity through several pathways, including releasing inflammatory cytokines to recruit adipose tissue macrophages (ATMs), stimulating lipogenesis, and changing metabolic capacity [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1-mediated miR-let-7g-5p triggers interlukin-6 and TNF-α to cause myopathy and chronic adipose inflammation in elderly patients with diabetes mellitus

Tsai

Huang

et al. 2022

Aging

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Background: Diabetes and sarcopenia are verified as mutual relationships, which seriously affect the quality of life of the elderly. Endothelin-1 is well investigated, is elevated in patients with diabetes, and is related to muscle cellular senescence and fibrosis. However, the mechanism of ET-1 between diabetes and myopathy is still unclear. The aim of this study was to evaluate the prevalence of sarcopenia in the elderly with diabetes and to clarify its relationship with ET-1 molecular biological mechanism, progress as well as changes in muscle and fat. Methods: We recruited 157 type 2 diabetes patients over 55 years old and investigated the prevalence of sarcopenia in diabetes patients and examined the association of ET-1 alterations with HbA1c, creatinine, or AMS/ht2. Next, sought to determine how ET-1 regulates inflammation in muscle cells by western blot and qPCR assay. Using XF Seahorse Technology, we directly quantified mitochondrial bioenergetics in 3T3-L1 cells. Results: ET-1 was positively correlated with HbA1c, creatinine levels, and duration of disease, and negatively correlated with AMS/ht2. We found that ET-1 dose-dependently induces tumor necrosis factor-α (TNF-α) and interleukin (IL)-6β expression through the PI3K/AKT, and NF-κB signaling pathways in C2C12 cells. Also identified that TNF-α, IL-6β, and visfatin releases were found in co-cultured with conditioned medium of ET-1/C2C12 in 3T3-L1 cells. ET-1 also reduces the energy metabolism of fat and induces micro-environment inflammation which causes myopathy. ET-1 also suppresses miR-let-7g-5p expression in myocytes and adipocytes. Conclusion: We describe a new mechanism of ET-1 triggering chronic inflammation in patients with hyperglycemia.

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Increased level of DNA damage in some organs of obese Zucker rats by γ‐H2AX analysis

Azzarà

Chiaramonte

Filomeni

et al. 2017

Environ and Mol Mutagen

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In a recent study, we showed that lymphocytes of obese Italian children/adolescents displayed levels of double strand breaks (DSB), assayed as serine 139-phosphorylated histone H2AX (γ-H2AX), about eightfold higher than normal weight controls, and that 30% of this damage-generated micronuclei. These findings suggested that obese children could be at increased risk of obesity-mediated cancer later in life. We therefore aimed to assess the level of γ-H2AX in a genetic animal model of obesity (Zucker rat) to identify a genotoxic/carcinogenic risk in some organs. The DSB marker was studied in 3- to 4-week-old rats and in 9- to 13-week-old rats. Paraffin-embedded sections of heart, thyroid, liver, pancreas, lung, kidney, esophagus, and gut from the fa-/fa- (obese) and the fa+/fa- (lean) control animals were processed for immunohistochemistry detection of γ-H2AX. Pancreas (0.0624 ± 0.0195), lung (0.1197 ± 0.0217), esophagus (0.1230 ± 0.0351), kidney (0.1546 ± 0.0149), and gut (0.1724 ± 0.0352) of 9- to 13-week-old obese rats showed a higher proportion of γ-H2AX-positive nuclei, than their lean counterparts (0.0092 ± 0.0033, 0.0416 ± 0.0185, 0.0368 ± 0.0088, 0.0686 ± 0.0318, and 0.0703 ± 0.0239, respectively). No difference was seen in the 3- to 4-week-old age group with regard to obesity, indicating that the DNA damage increased with older age of the rats. We hypothesize that the organs of the obese animals showing high levels of DSB could represent target tissues for the development of obesity-related cancers. Environ. Mol. Mutagen. 58:477-484, 2017. © 2017 Wiley Periodicals, Inc.

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Transcriptional Alterations of ET-1 Axis and DNA Damage in Lung Tissue of a Rat Obesity Model

Cited by 5 publications

References 37 publications

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population

Endothelin-1-mediated miR-let-7g-5p triggers interlukin-6 and TNF-α to cause myopathy and chronic adipose inflammation in elderly patients with diabetes mellitus

Increased level of DNA damage in some organs of obese Zucker rats by γ‐H2AX analysis

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