Endogenous estradiol and inflammation biomarkers: potential interacting mechanisms of obesity-related disease

Eldridge, Ronald C.; Wentzensen, Nicolas; Pfeiffer, Ruth M.; Brinton, Louise A.; Hartge, Patricia; Guillemette, Chantal; Kemp, Troy J.; Pinto, Lígia A.; Trabert, Britton

doi:10.1007/s10552-020-01280-6

Cited by 18 publications

(17 citation statements)

References 63 publications

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“…Finally, our findings cannot be extended to the population with mild and moderate OSAS because of our exclusion criteria. Thereafter, although the data on the reduction of CRP levels is a very interesting finding, our sample of patients is made up of almost 37% women and CRP is a marker of non-specific inflammation possibly linked with endogenous estradiol [ 46 ]. Therefore, the complex link between estradiol and inflammation may influence the result.…”

Section: Discussionmentioning

confidence: 99%

Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study

et al. 2021

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“…Females have higher CRP concentrations than men, which may be hormonal, that is, female CRP concentrations correlate positively with estradiol levels, and the odds of CRP falling above the median doubles with each standard deviation increment in endogenous estradiol ( Eldridge et al, 2020 ). Higher female CRP may explain the greater estimated heritability we observed in female than male offspring (0.13 vs. 0.08) and female than male sibling (0.20 vs. 0.10), the greater heritability of untransformed CRP in females than males reported by Friedlander et al (2006) (0.352 vs. 0.150), and the higher within-pair correlations in female than male MZ twins reported by Retterstol, Eikvar & Berg (2003) ( r = 0.44 vs. r = 0.31).…”

Section: Discussionmentioning

confidence: 99%

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

Williams¹

2021

PeerJ

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Background “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities (h2) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. Methods Serum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (βFS, h2 ={(1 + 8rspouseβFS)0.5 − 1}/(2rspouse)) and offspring-parent regression slopes (βOP, h2 = 2βOP/(1 + rspouse)) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. Results Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from βOP (Ptrend = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from βFS (Ptrend = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. Conclusion Heritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF-α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.

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“…E2 seems to play a crucial role in inflammatory processes ( 47 , 48 ), and both pro-inflammatory as well as anti-inflammatory effects of E2 have been described ( 49 , 50 ). In the present study, E2 treatment upregulated the expression of the pro-inflammatory markers, e.g., TNF-α, c-fos, and NFκB, in male M1 macrophages in a pro-inflammatory environment (LPS treatment), whereas it reduced the expression of the anti-inflammatory MCP-1 in male M2 macrophages exposed to an anti-inflammatory environment (IL4/IL13 treatment), suggesting that E2 promotes pro-inflammatory responses in male macrophages.…”

Section: Discussionmentioning

confidence: 99%

Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli

et al. 2021

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Mounting evidence argues for the significant impact of sex in numerous cardiac pathologies, including myocarditis. Macrophage polarization and activation of cardiac fibroblasts play a key role in myocardial inflammation and remodeling. However, the role of sex in these processes is still poorly understood. In this study, we investigated sex-specific alterations in the polarization of murine bone marrow-derived macrophages (BMMs) and the polarization-related changes in fibroblast activation. Cultured male and female murine BMMs from C57/BL6J mice were polarized into M1 (LPS) and M2 (IL-4/IL-13) macrophages. Furthermore, male and female cardiac fibroblasts from C57/BL6J mice were activated with TNF-α, TGF-β, or conditioned medium from M1 BMMs. We found a significant overexpression of M1 markers (c-fos, NFκB, TNF-α, and IL-1β) and M2 markers (MCP-1 and YM1) in male but not female activated macrophages. In addition, the ROS levels were higher in M1 male BMMs, indicating a stronger polarization. Similarly, the pro-fibrotic markers TGF-β and IL-1β were expressed in activated cardiac male fibroblasts at a significantly higher level than in female fibroblasts. In conclusion, the present study provides strong evidence for the male-specific polarization of BMMs and activation of cardiac fibroblasts in an inflammatory environment. The data show an increased inflammatory response and tissue remodeling in male mice.

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Endogenous estradiol and inflammation biomarkers: potential interacting mechanisms of obesity-related disease

Cited by 18 publications

References 63 publications

Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study

Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli

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