Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

Objective. Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2) would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery.Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis) and liver biopsies (RT-PCR gene expression) were obtained from 91 women during surgery.Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P<0.01) and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (allP<0.05). While plasma ASP was lower in pre- versus postmenopausal women (P<0.01), the hepatic C5L2/C5aR mRNA ratio was increased (P<0.001) and correlated positively with estrone (P<0.01) and estradiol (P<0.001) and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (allP<0.05). Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT,P<0.05, AST and GGT,P<0.0012-way-ANOVA).Conclusion. C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

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Distinct Metabolic Profile in Early Pregnancy of Overweight and Obese Women Developing Gestational Diabetes

Journal of Nutrition ◽

10.1093/jn/nxz220 ◽

2019 ◽

Vol 150 (1) ◽

pp. 31-37 ◽

Cited By ~ 5

Author(s):

Kati Mokkala ◽

Tero Vahlberg ◽

Outi Pellonperä ◽

Noora Houttu ◽

Ella Koivuniemi ◽

...

Keyword(s):

Amino Acids ◽

Gestational Diabetes ◽

Pregnant Women ◽

Early Pregnancy ◽

Metabolic Profile ◽

Medical Condition ◽

Oral Glucose ◽

Low Grade ◽

Obese Women ◽

Characteristic Analysis

ABSTRACT Background Reliable biomarkers for gestational diabetes mellitus (GDM) would be beneficial in the early prevention of adverse metabolic outcomes during pregnancy and beyond. Objectives The objective of this study was to investigate whether the early pregnancy serum metabolic profile differs in women developing GDM from those remaining healthy. Furthermore, we evaluated the potential of these metabolites to act as predictive markers for GDM. Methods This was a prospective study investigating overweight and obese [prepregnancy BMI (in kg/m2) ≥25 and >30, respectively] pregnant women (prepregnancy median BMI: 28.5; IQR: 26.4–31.5; n = 357). Fasting serum samples were analyzed with a targeted NMR approach in early pregnancy (median: 14.3 weeks of gestation). GDM was diagnosed on the basis of a 2-h, 75-g oral-glucose-tolerance test at a median of 25.7 weeks of gestation. Results In early pregnancy, 78 lipid metabolites differed in women who later developed GDM (n = 82) compared with those who remained healthy (n = 275) (ANCOVA, adjusted for confounding factors and corrected for multiple comparisons; false discovery rate <0.05). Higher concentrations of several-sized VLDL particles and medium- and small-sized HDL particles, and lower concentrations of very large-sized HDL particles, were detected in women developing GDM. Furthermore, concentrations of amino acids including 2 branched-chain amino acids, isoleucine and leucine, and GlycA, a marker for low-grade inflammation, were higher in women who developed GDM. Receiver operating characteristic analysis revealed that the most predictive marker for GDM was a higher concentration of small-sized HDL particles (AUC: 0.71; 95% CI: 0.67, 0.77; P < 0.001). Conclusions We identified a distinct early pregnancy metabolomic profile especially attributable to small HDL particles in women developing GDM. The aberrant metabolic profile could represent a novel way to allow early identification of this most common medical condition affecting pregnant women. This trial was registered at clinicaltrials.gov as NCT01922791.

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Epidemiology and (Patho)Physiology of Folic Acid Supplement Use in Obese Women before and during Pregnancy

Nutrients ◽

10.3390/nu13020331 ◽

2021 ◽

Vol 13 (2) ◽

pp. 331

Author(s):

Melissa van der Windt ◽

Sam Schoenmakers ◽

Bas van Rijn ◽

Sander Galjaard ◽

Régine Steegers-Theunissen ◽

...

Keyword(s):

Folic Acid ◽

Scientific Evidence ◽

Folate Deficiency ◽

Folate Intake ◽

Low Grade ◽

Obese Women ◽

Folic Acid Supplement ◽

Physiological Uptake ◽

Supplement Use ◽

Acid Supplement

Preconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status, lifestyle, and medical conditions.

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Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein

Molecules ◽

10.3390/molecules26041070 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1070

Author(s):

Sabina Cauci ◽

Serena Xodo ◽

Cinzia Buligan ◽

Chiara Colaninno ◽

Mattia Barbina ◽

...

Keyword(s):

Oxidative Stress ◽

High Sensitivity ◽

Low Grade ◽

Strong Positive Correlation ◽

Obese Women ◽

C Reactive Protein ◽

Oxidative Stress Biomarkers ◽

Free Oxygen Radical ◽

Reactive Protein ◽

Healthy Women

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p < 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, p < 0.001. Hydroperoxides were strongly positively correlated to hsCRP in all women (rs = 0.622, p < 0.001), in OC-users (rs = 0.442, p < 0.001), and in non-OC-users (rs = 0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.

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Increased Plasma Ferritin Concentration and Low-Grade Inflammation—A Mendelian Randomization Study

Clinical Chemistry ◽

10.1373/clinchem.2017.276055 ◽

2018 ◽

Vol 64 (2) ◽

pp. 374-385 ◽

Cited By ~ 13

Author(s):

Ingrid W Moen ◽

Helle K M Bergholdt ◽

Thomas Mandrup-Poulsen ◽

Børge G Nordestgaard ◽

Christina Ellervik

Keyword(s):

Odds Ratio ◽

Mendelian Randomization ◽

Iron Concentration ◽

Complement C3 ◽

Incomplete Penetrance ◽

Low Grade ◽

Ferritin Concentration ◽

Mediation Analyses ◽

All Cause Mortality ◽

Low Grade Inflammation

Abstract BACKGROUND It is unknown why increased plasma ferritin concentration predicts all-cause mortality. As low-grade inflammation and increased plasma ferritin concentration are associated with all-cause mortality, we hypothesized that increased plasma ferritin concentration is genetically associated with low-grade inflammation. METHODS We investigated whether increased plasma ferritin concentration is associated with low-grade inflammation [i.e., increased concentrations of C-reactive protein (CRP) and complement component 3 (C3)] in 62537 individuals from the Danish general population. We also applied a Mendelian randomization approach, using the hemochromatosis genotype C282Y/C282Y as an instrument for increased plasma ferritin concentration, to assess causality. RESULTS For a doubling in plasma ferritin concentration, the odds ratio (95% CI) for CRP ≥2 vs <2 mg/L was 1.12 (1.09–1.16), with a corresponding genetic estimate for C282Y/C282Y of 1.03 (1.01–1.06). For a doubling in plasma ferritin concentration, odds ratio (95% CI) for complement C3 >1.04 vs ≤1.04 g/L was 1.28 (1.21–1.35), and the corresponding genetic estimate for C282Y/C282Y was 1.06 (1.03–1.12). Mediation analyses showed that 74% (95% CI, 24–123) of the association of C282Y/C282Y with risk of increased CRP and 56% (17%–96%) of the association of C282Y/C282Y with risk of increased complement C3 were mediated through plasma ferritin concentration. CONCLUSIONS Increased plasma ferritin concentration as a marker of increased iron concentration is associated observationally and genetically with low-grade inflammation, possibly indicating a causal relationship from increased ferritin to inflammation. However, as HFE may also play an immunological role indicating pleiotropy and as incomplete penetrance of C282Y/C282Y indicates buffering mechanisms, these weaknesses in the study design could bias the genetic estimates.

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Effects of a weight loss program on body composition and the metabolic profile in obese postmenopausal women displaying various obesity phenotypes: a MONET group study

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0451 ◽

2015 ◽

Vol 40 (7) ◽

pp. 695-702 ◽

Cited By ~ 2

Author(s):

Eve Normandin ◽

Eric Doucet ◽

Rémi Rabasa-Lhoret ◽

Martin Brochu

Keyword(s):

Weight Loss ◽

Body Composition ◽

Postmenopausal Women ◽

Body Fat ◽

Metabolic Profile ◽

Fat Distribution ◽

Weight Loss Program ◽

Glucose Disposal ◽

Fasting Insulin ◽

Secondary Analyses

Obesity is a heterogeneous condition, since the metabolic profile may differ greatly from one individual to another. The objective of this study was to compare the effect of a 6-month diet-induced weight loss program on body composition and the metabolic profile in obese individuals displaying different obesity phenotypes. Secondary analyses were done on 129 obese (% body fat: 46% ± 4%) postmenopausal women (age: 57 ± 4 years). Outcome measures included body composition, body fat distribution, glucose homeostasis, fasting lipids, and blood pressure. Obesity phenotypes were determined based on lean body mass (LBM) index (LBMI = LBM/height2) and visceral fat (VF) accumulation, as follows: 1, lower VF and lower LBMI (n = 35); 2, lower VF and higher LBMI (n = 19); 3, higher VF and lower LBMI (n = 14); and 4, higher VF and higher LBMI (n = 61). All groups had significantly improved measures of body composition after the intervention (P < 0.0001). Greater decreases in LBM and LBMI were observed in the higher LBMI groups than in the lower LBMI groups (P < 0.0001). Similarly, decreases in VF were greater in the higher VF groups than in the lower VF groups (P < 0.05). Overall, fasting insulin levels and glucose disposal improved following the intervention, with higher LBMI groups showing a trend for greater improvements (P = 0.06 and 0.07, respectively). Overall, no difference was observed among the different obesity phenotypes regarding improvements in the metabolic profile in response to weight loss. Individuals displaying higher VF or higher LBMI at baseline experienced significantly greater decreases for these variables after the intervention.

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Green Cardamom Plus Low Calorie Diet Can Decrease Inflammatory Genes Expression Among Obese Women With Poly Cystic Ovarian Syndrome, A Double Blind Randomized Clinical Trial

10.21203/rs.3.rs-245937/v1 ◽

2021 ◽

Author(s):

Sahar Cheshmeh ◽

Maysa Ghayyem ◽

Firoozeh Khamooshi ◽

Neda Heydarzadeh ◽

Niloofar Hojati ◽

...

Keyword(s):

Expression Level ◽

Low Grade ◽

Obese Women ◽

Double Blind ◽

Low Calorie ◽

Low Calorie Diet ◽

Genes Expression ◽

Tnf Α ◽

Calorie Diet ◽

Green Cardamom

Abstract PurposePolycystic ovary syndrome (PCOS) is a common cause of endocrine disorder and infertility among womenin which is related with low grade inflammation. Therefore, this current randomized, double-blind, placebo-controlledclinical trial assessed the effects of green cardamom supplementation on inflammatory markers and gene expressionamong obese women with PCOS.MethodsWe included 194 obese PCOS women that gave all of them low calorie diet. These subjects were randomlydivided in two studied groups including intervention with 3 g/day green cardamom (n=99) and placebo groups (n=95).Anthropometric indices, androgen hormones, and inflammatory factors (tumor necrosis factor-a (TNF-α), Interleukin6 (IL-6), and C- reactive protein (CRP)) were assessed before and after four months intervention. Their TNF-α, IL-6,and CRP genes expression level were measured using reverse transcription-polymerase chain reaction (RT-PCR)method.ResultsAnthropometric indices were improved in both two studied groups (P<0.001). Among androgen hormonesluteinizing hormone, androstenedione, and dehydroepiandrosterone were significantly decreased (P<0.001), as wellas, follicle-stimulating hormone was significantly increased (P<0.001) in the green cardamom group. Our findingsshowed that TNF-α, IL-6, and CRP serum were significantly decreased after the intervention with green cardamomplus low calorie diet (P<0.001). In addition, the expression level of TNF-α and CRP genes were significantly decreasedin intervention groups (P<0.001).ConclusionsThis present study support the beneficial anti-inflammatory effect of green cardamom on theinflammatory status in the PCOS women.Level of evidenceLevel I, randomized clinical trialTrial registrationThis trial was registered with the Iranian Clinical Trials Registry (registration number:IRCT20200608047697N1). 1 August, 2020; https://www.irct.ir/trial/48748

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High-risk HPV genotypes and cervical lesions association in postmenopausal women

European Journal of Public Health ◽

10.1093/eurpub/ckab120.044 ◽

2021 ◽

Vol 31 (Supplement_2) ◽

Author(s):

Ana Rita Fernandes Miranda da Costa ◽

Cláudia Sousa ◽

Erica Isidoro ◽

Regina Silva ◽

Cristiana Mourato

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Postmenopausal Women ◽

Age Groups ◽

Low Grade ◽

High Grade ◽

Cervical Lesions ◽

Intraepithelial Lesion ◽

The Bethesda System ◽

High Risk Hpv

Abstract Background Persistent infection by high-risk Human Papillomavirus (hrHPV) are the major cause of cervical cancer. Studies report disparities in the incidence of infection and the various genotypes of this virus in different age groups, suggesting a higher frequency of hrHPV in young women and low-risk subtypes being predominant in older women. This study aimed to investigate the incidence and distribution of hrHPV genotypes in postmenopausal women as well as the correlation with the cytological findings. Methods 16 859 women, aged 50–64 years, performed cervical cancer screening test in Friuri Venezia Giulia region, Italy. The infection was evaluated by the Polymerase Chain Reaction methodology and the positive samples were evaluated by Liquid Based Cytology according to the Bethesda System from 2014. A statistical analysis was performed to study the molecular and cytological data of this population. Results hrHPV infection were found in 5.8% of the women and 78.3% of these were caused by hrHPV other than HPV16 and HPV18 (). Also, 65.7% of the positive samples were negative for intraepithelial lesion or malignancy while low grade squamous intraepithelial lesion was the most frequent (22.4%). There was an increase in the number of high-grade intraepithelial lesions in the presence of HPV16 compared to that recorded when this genotype was absent (20.8% vs. 8.5%). No cervical cancers were detected. Conclusions Infection with hrHPV is uncommon in postmenopausal women and it is mostly caused by subtypes less associated with the development of cervical cancer. Yet, HPV16 infection triggers the development of high-grade lesions.

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Evaluation of cervicovaginal smear results at postmenopausal period

Advances in Modern Oncology Research ◽

10.18282/amor.v2.i1.64 ◽

2016 ◽

Vol 2 (1) ◽

Author(s):

Sefa Kelekci ◽

Emre Destegül ◽

Servet Gençdal ◽

Emre Ekmekçi ◽

Hüseyin Aydoğmuş ◽

...

Keyword(s):

Postmenopausal Women ◽

Pap Smear ◽

Premalignant Lesions ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Screening Programs ◽

Postmenopausal Period ◽

Pap Smear Screening ◽

Intraepithelial Lesion

<p>This study evaluates the statistical analysis of cervicovaginal smear results at postmenopausal period accompanied by literature. Cervicovaginal smear results of 894 postmenopausal women were evaluated retrospectively according to the 2001 Bethesda system (BS) in Adana Numune Training and Research Hospital of Obstetrics and Gynecology Clinic from 2007–2010. The study found, normal results on 287 patients (32.1%), benign findings on 556 patients (62.2%), abnormal epithelial cell changes on 48 patients (5.36%) and malignant changes on 3 patients (0.33%). The abnormal epithelial changes were observed to be atypical cells of undetermined significance (ASC-US) for 22 patients (2.46%), <a href="http://medical-dictionary.thefreedictionary.com/high-grade+squamous+intraepithelial+lesion">low-grade squamous intraepithelial lesion</a> (LSIL) for 11 patients (1.23%), <a href="http://medical-dictionary.thefreedictionary.com/high-grade+squamous+intraepithelial+lesion">high-grade squamous intraepithelial lesion</a> (HSIL) for 7 patients (0.78%), findings that cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) for 6 patients (0.55%) and atypical glandular cells-not otherwise specified (AGC-NOS) for 2 patients (0.22%). Malignant results were 2 squamous cell carcinomas (SCC) (0.22%) and 1 adenocarcinoma (ACC) (0.11%). Cervical cancer screening programs should be expanded and Pap smear screening should be applied to all postmenopausal women. The longer time span involved from premalignant lesions to cancer improves our chance for the diagnosis and treatment. As the incidence of invasive cancer increases in menopausal period, gynecological smear examination and regular check-up are crucial. A high rate of abnormalities of epithelial cells was detected in this study.</p><p> </p>

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Aerobic training improved low-grade inflammation in obese women with intellectual disability

Journal of Intellectual Disability Research ◽

10.1111/jir.12056 ◽

2013 ◽

Vol 58 (6) ◽

pp. 583-590 ◽

Cited By ~ 15

Author(s):

F. J. Ordonez ◽

M. A. Rosety ◽

A. Camacho ◽

I. Rosety ◽

A. J. Diaz ◽

...

Keyword(s):

Intellectual Disability ◽

Aerobic Training ◽

Low Grade ◽

Obese Women ◽

Low Grade Inflammation

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Comparative Study of Chemerin and Inflammatory markers between Obese with Insulin Resistance and lean healthy women

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00630 ◽

2021 ◽

pp. 3647-3650

Author(s):

Moushira Zaki ◽

Sanaa Kamal ◽

Mona Abd Elmotaleb A. Hussein ◽

Hend M. Tawfeek ◽

Mina Wassef Girgiss ◽

...

Keyword(s):

Insulin Resistance ◽

Inflammatory Marker ◽

Neutrophil To Lymphocyte Ratio ◽

Metabolic Parameters ◽

Low Grade ◽

Obese Women ◽

Fat Percentage ◽

Inflammatory Biomarker ◽

Lymphocyte Ratio ◽

Healthy Women

Background: Chemerin has been newly defined to be released from mature adipocytes and the chemerin concentrations in human serum augmented with obesity. There is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. The aim of this study is to expound the prospective role of chemerin the in inflammation. Also, investigate relation between chemerin and serum lipid, glucose, body fat percentage, and metabolic parameters in obese and lean women with IR. Lymphocytes and neutrophils play a major role in inflammation and comprise the first line of defense against infection. The ratio of absolute neutrophil count to lymphocyte count, the neutrophil-to-lymphocyte ratio (NLR), determined as is a novel inflammatory biomarker utilized as a prognostic factor in numerous diseases Methods: This study was designed to investigate serum chemerin, NLR, and high-sensitive C-reactive protein (hsCRP) levels in 50 obese women with IR and 50 lean healthy women. Results: Obese group had significant higher levels of serum chemerin, NLR, hsCRP levels and metabolic parameters than lean one. Chemerin also correlated positively with NLR inflammatory marker and body mass index (BMI). Neutrophil‐to‐lymphocyte ratio was related to pro‐inflammatory Conclusion: The present study elucidates that chemerin levels are concomitant with obesity and IR and could play a role in the inflammation, having key aspects of metabolic syndrome.

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