scholarly journals Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1732
Author(s):  
Francesca Parisi ◽  
Roberta Milazzo ◽  
Valeria M. Savasi ◽  
Irene Cetin

Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 934 ◽  
Author(s):  
Gabriela E. Leghi ◽  
Merryn J. Netting ◽  
Philippa F. Middleton ◽  
Mary E. Wlodek ◽  
Donna T. Geddes ◽  
...  

Maternal obesity has been associated with changes in the macronutrient concentration of human milk (HM), which have the potential to promote weight gain and increase the long-term risk of obesity in the infant. This article aimed to provide a synthesis of studies evaluating the effects of maternal overweight and obesity on the concentrations of macronutrients in HM. EMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science, and ProQuest databases were searched for relevant articles. Two authors conducted screening, data extraction, and quality assessment independently. A total of 31 studies (5078 lactating women) were included in the qualitative synthesis and nine studies (872 lactating women) in the quantitative synthesis. Overall, maternal body mass index (BMI) and adiposity measurements were associated with higher HM fat and lactose concentrations at different stages of lactation, whereas protein concentration in HM did not appear to differ between overweight and/or obese and normal weight women. However, given the considerable variability in the results between studies and low quality of many of the included studies, further research is needed to establish the impact of maternal overweight and obesity on HM composition. This is particularly relevant considering potential implications of higher HM fat concentration on both growth and fat deposition during the first few months of infancy and long-term risk of obesity.


2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
R. C. M. Adams ◽  
C. Smith

Changes in the in utero environment result in generational transfer of maladapted physiology in the context of conditions such as stress, obesity, and anxiety. Given the significant contribution of noncommunicable diseases—which are characterised by chronic inflammation—to population mortality, the potential for chronic maternal inflammation mediating foetal programming is a growing concern. The extent of generational transfer in terms of immune functionality and leukocyte glucocorticoid sensitivity was investigated over two generations of offspring (F1 and F2) in a model of chronic LPS-induced maternal inflammation in C57/BL/6 mice. Maternal inflammation resulted in glucocorticoid hypersensitivity (increased glucocorticoid receptor expression levels) in the majority of leukocyte subpopulations in both F1 and F2 offspring. Furthermore, splenocytes stimulated with LPS in vitro exhibited exacerbated inflammatory cytokine responses, which were even more prominent in F2 than F1; this effect could be ascribed to NLRP3 inflammasome hyperactivity in F1 but not F2. Current data illustrates that parental chronic inflammation may mediate the inflammatory profile in offspring, potentially propagating a maladapted proinflammatory phenotype in subsequent generations.


Author(s):  
Laetitia Delort ◽  
Juliette Cholet ◽  
Caroline Decombat ◽  
Marion Vermerie ◽  
Charles Dumontet ◽  
...  

Breast cancer is the most common cancer among women worldwide. Overweight and obesity are now recognized as established risk factors for this pathology in postmenopausal women. These conditions are also believed to be responsible for higher recurrence and mortality rates. Reciprocal interactions have been described between adipose and cancer cells. An adipose microenvironment favors a greater proliferation of cancer cells, their invasion and even resistance to anti-cancer treatments. In addition, the chronic low-grade inflammation observed in obese individuals is believed to amplify these processes. Among the cell types present in the breast, myoepithelial cells (MECs), located at the interface of the epithelial cells and the stroma, are considered “tumor suppressor” cells. During the transition from ductal carcinoma in situ to invasive cancer, disorganization or even the disappearance of MECs is observed, thereby enhancing the ability of the cancer cells to migrate. As the adipose microenvironment is now considered as a central actor in the progression of breast cancer, our objective was to evaluate if it could be involved in MEC functional modifications, leading to the transition of in situ to invasive carcinoma, particularly in obese patients. Through a co-culture model, we investigated the impact of human adipose stem cells from women of normal weight and obese women, differentiated or not into mature adipocytes, on the functionality of the MECs by measuring changes in viability, apoptosis, gene, and miRNA expressions. We found that adipose cells (precursors and differentiated adipocytes) could decrease the viability of the MECs, regardless of the original BMI. The adipose cells could also disrupt the expression of the genes involved in the maintenance of the extracellular matrix and to amplify the expression of leptin and inflammatory markers. miR-122-5p and miR-132-3p could also be considered as targets for adipose cells. The metabolite analyses revealed specific profiles that may be involved in the growth of neoplastic cells. All of these perturbations could thus be responsible for the loss of tumor suppressor status of MECs and promote the transition from in situ to invasive carcinoma.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 773-773
Author(s):  
Gabriela Leghi ◽  
Merryn J Netting ◽  
Philippa F Middleton ◽  
Mary E Wlodek ◽  
Donna T Geddes ◽  
...  

Abstract Objectives This article aimed to provide a synthesis of studies evaluating the effects of maternal overweight and obesity, including body mass index (BMI) and other measures of adiposity, on the concentrations of macronutrients (fat, protein and lactose) in human milk (HM). Methods EMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science and ProQuest databases were searched for relevant articles. Two authors conducted screening, data extraction and quality assessment independently. Meta-analyses of eligible studies were conducted using Review Manager software version 5.3. Results A total of 31 studies (5078 lactating women) were included in the qualitative synthesis and 9 studies (872 lactating women) in the quantitative synthesis. The meta-analysis indicated that maternal overweight and obesity were associated with higher concentrations of fat in mature HM (p = 0.01) and lactose in colostrum (p = 0.002). While the qualitative analyses broadly supported the findings of the meta-analysis, the qualitative assessment identified considerable variability in the results between studies and low quality of many of the included studies, making it difficult to draw robust conclusions. Conclusions Overall, maternal BMI and adiposity measurements were associated with differences in the concentrations of fat and lactose in HM, however the direction of change was dependent on the stage of lactation, whereas protein concentration in HM did not appear to differ between overweight and/or obese and normal weight women. This is particularly relevant considering potential implications of higher HM fat concentration on both growth and fat deposition during the first few months of infancy and long-term risk of obesity. Funding Sources GEL was supported by a FOODplus Early Life Nutrition Scholarship, The University of Adelaide. BSM received a Career Development Award from the National Health and Medical Research Council of Australia (NHMRC).


2020 ◽  
Author(s):  
Albina Tskhay ◽  
Alena Yezhova ◽  
Kenneth Alibek

Abstract Background. Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19. Method. Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries population, was conducted. Results. A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries. Conclusion. The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.


2017 ◽  
Vol 8 (5) ◽  
pp. 529-540 ◽  
Author(s):  
S. A. Segovia ◽  
M. H. Vickers ◽  
C. M. Reynolds

Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.


2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Author(s):  
Esther Rodríguez-Gallego ◽  
Marta Riera-Borrull ◽  
Anna Hernández-Aguilera ◽  
Roger Mariné-Casadó ◽  
Anna Rull ◽  
...  

Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristina Schaedlich ◽  
Laura-Sophie Beier ◽  
Judith Kolbe ◽  
Martin Wabitsch ◽  
Jana Ernst

AbstractIn the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson–Golabi–Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)–d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.


Author(s):  
Chaitanya A. Shembekar ◽  
Shantanu C. Shembekar ◽  
Manisha C. Shembekar ◽  
Parul Sharma Saoji ◽  
Jayshree J. Upadhye

Background: Overweight, obesity, and morbid obesity in the mother are associated with adverse obstetrics well as neonatal outcome. Aim of this study was to assess the prevalence of overweight and obesity, and the impact of body mass index (BMI) on maternal and neonatal outcome.Methods: This is a retrospective study from January 2018 to September 2018 on 180 women with singleton term pregnancies. Maternal and neonatal outcomes at delivery were noted.Results: In present study, 3 (1.66%) pregnant women were underweight, 57 (31.66%) pregnant women had normal BMI, 71 (39.44%) pregnant women were overweight while 49 (27.22%) pregnant women were obese. Gestational weight gain was less than 8 kgs in 40 (22.22%) pregnant women, weight gain was 8-15.9 kgs in 132 (73.33%) pregnant women while weight gain was more than 16 kgs in 8 (4.44%) pregnant women. Out of 3 underweight women, 1 delivered by cesarean section and 2 had normal delivery, out of 57 women with normal BMI, 21 delivered by cesarean section and 36 had normal delivery, out of 71 overweight women, 47 delivered by cesarean section and 34 had normal delivery while out of 49 obese women, 38 delivered by cesarean section and 11 had normal delivery. PET and GDM was seen in 9 (7.5%) women each while macrosomia were seen in 5 (4.16%) women.Conclusions: Increased association was seen with maternal obesity and adverse outcome of pregnancy like PIH, GDM, cesarean section.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4378
Author(s):  
Hidde P. van Steenwijk ◽  
Aalt Bast ◽  
Alie de Boer

Background and aims: In recent years, it has become clear that low-grade chronic inflammation is involved in the onset and progression of many non-communicable diseases. Many studies have investigated the association between inflammation and lycopene, however, results have been inconsistent. This systematic review aims to determine the impact of circulating lycopene on inflammation and to investigate the effect of consuming tomato products and/or lycopene supplements on markers of inflammation. Methods: Eligible studies, published before March 2020, were identified from PubMed, EBSCOhost and ScienceDirect. Human studies published in English, that evaluated the effect of circulating lycopene in relation to inflammation biomarkers were screened and included. Studies assessing lycopene intake or general intake of carotenoids/antioxidants without measuring circulating lycopene, as well as those not reporting inflammation biomarkers as outcomes, were excluded. Results: Out of 80 publications identified and screened, 35 met the inclusion criteria. Results from 18 cross-sectional studies suggest that lycopene levels are adversely affected during inflammation and homeostatic imbalance. Most of the 17 included intervention studies reported increased circulating lycopene levels after tomato/lycopene supplementation, but almost no changes in inflammation biomarkers were observed. Conclusions: There is little evidence that increasing tomato intake or lycopene supplementation diminuates this inflammation. However, depletion of lycopene may be one of the first signs of low-grade inflammation. The available data thereby imply that it is beneficial to consume lycopene-rich foods occasionally to stay healthy and keep circulating lycopene at a basal level.


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