Inflammasomes in the Pathophysiology of Maternal Obesity: Potential Therapeutic Targets to Reduce Long-Term Adverse Health Outcomes in the Mother and Offspring

2020 ◽  
Vol 19 (2) ◽  
pp. 165-175
Author(s):  
Padma Murthi ◽  
Gayathri Rajaraman
Keyword(s):  
Health Outcomes ◽  
Molecular Mechanisms ◽  
Maternal Obesity ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Reproductive Age ◽  
Adverse Health ◽  
Adverse Health Outcomes ◽  
Self Assembling ◽  
Prevalence Of Obesity

: Over the past 20 years, the prevalence of obesity has risen dramatically worldwide, with an increase in occurrence among women in their reproductive age. Obesity during pregnancy is associated with significantly increased maternal and fetal morbidity and mortality. In addition to the short-term adverse health outcomes, both mother and the child are prone to develop cardiovascular, metabolic and neurological disorders. Although associations between obesity during pregnancy and adverse maternalfetal health outcomes are clear, the complex molecular mechanisms underlying maternal obesity remain largely unknown. This review describes multimeric self-assembling protein complexes, namely inflammasomes, as potential molecular targets in the pathophysiology of maternal obesity. Inflammasomes are implicated in both normal physiological and in pathophysiological processes that occur in response to an inflammatory milieu throughout gestation. This review highlights the current knowledge of inflammasome expression and its activity in pregnancies affected by maternal obesity. Key discussions in defining pharmacological inhibition of upstream as well as downstream targets of the inflammasome signaling cascade; and the inflammasome platform, as a potential therapeutic strategy in attenuating the pathophysiology underpinning inflammatory component in maternal obesity are presented herein.

scholarly journals Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2768
Author(s):  
Livia Belcastro ◽  
Carolina S. Ferreira ◽  
Marcelle A. Saraiva ◽  
Daniela B. Mucci ◽  
Antonio Murgia ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Birth Weight ◽  
Molecular Mechanisms ◽  
Maternal Obesity ◽  
Fold Increase ◽  
Reproductive Age ◽  
Obese Women ◽  
Fatty Acid Transporter ◽  
Prevalence Of Obesity

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexahenoic acid (DHA), neuroprostanes, arachidonic acid (AA), and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.

scholarly journals Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity

2021 ◽  
Author(s):  
Livia Belcastro ◽  
Carolina S. Ferreira ◽  
Marcelle A. Saraiva ◽  
Daniela B. Mucci ◽  
Antonio Murgia ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Birth Weight ◽  
Molecular Mechanisms ◽  
Maternal Obesity ◽  
Reproductive Age ◽  
Obese Women ◽  
Fatty Acid Transporter ◽  
Prevalence Of Obesity

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

scholarly journals The effects of assisted reproduction technologies on metabolic health and disease

2020 ◽  
Author(s):  
Maria Florencia Heber ◽  
Grażyna Ewa Ptak
Keyword(s):  
Metabolic Syndrome ◽  
Health Outcomes ◽  
Metabolic Diseases ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Postnatal Life ◽  
Metabolic Alterations ◽  
Adverse Health ◽  
Adverse Health Outcomes ◽  
The Individual

Abstract Background The increasing prevalence of metabolic diseases places a substantial burden on human health throughout the world. It is believed that predisposition to metabolic disease starts early in life, a period of great susceptibility to epigenetic reprogramming due to environmental insults. Assisted reproductive technologies (ART), i.e., treatments for infertility, may affect embryo development, resulting in multiple adverse health outcomes in postnatal life. The most frequently observed alteration in ART pregnancies is impaired placental nutrient transfer. Moreover, consequent intrauterine growth restriction and low birth weight followed by catch-up growth can all predict future obesity, insulin resistance, and chronic metabolic diseases. Scope of the review In this review, we have focused on evidence of adverse metabolic alterations associated with ART, which can contribute to the development of chronic adult-onset diseases, such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Due to high phenotypic plasticity, ART pregnancies can produce both offspring with adverse health outcomes, as well as healthy individuals. We further discuss the sex-specific and age-dependent metabolic alterations reflected in ART offspring, and how the degree of interference of a given ART procedure (from mild to more severe manipulation of the egg) affects the occurrence and degree of offspring alterations. Major conclusions Over the last few years, studies have reported signs of cardiometabolic alterations in ART offspring that are detectable at a young age but that do not appear to constitute a high risk of disease and morbidity per se. These abnormal phenotypes could be early indicators of the development of chronic diseases, including metabolic syndrome, in adulthood. The early detection of metabolic alterations could contribute to preventing the onset of disease in adulthood. Such early interventions may counteract the risk factors and improve the long-term health of the individual.

scholarly journals Understanding the influence of socioeconomic status on the association between combinations of lifestyle factors and adverse health outcomes: a systematic review protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e042212
Author(s):  
Hamish Foster ◽  
Peter Polz ◽  
Frances Mair ◽  
Jason Gill ◽  
Catherine A O'Donnell
Keyword(s):  
Systematic Review ◽  
Socioeconomic Status ◽  
Health Outcomes ◽  
Meta Analysis ◽  
Lifestyle Factors ◽  
Lifestyle Factor ◽  
Unhealthy Lifestyle ◽  
Adverse Health ◽  
Adverse Health Outcomes ◽  
The Impact

IntroductionCombinations of unhealthy lifestyle factors are strongly associated with mortality, cardiovascular disease (CVD) and cancer. It is unclear how socioeconomic status (SES) affects those associations. Lower SES groups may be disproportionately vulnerable to the effects of unhealthy lifestyle factors compared with higher SES groups via interactions with other factors associated with low SES (eg, stress) or via accelerated biological ageing. This systematic review aims to synthesise studies that examine how SES moderates the association between lifestyle factor combinations and adverse health outcomes. Greater understanding of how lifestyle risk varies across socioeconomic spectra could reduce adverse health by (1) identifying novel high-risk groups or targets for future interventions and (2) informing research, policy and interventions that aim to support healthy lifestyles in socioeconomically deprived communities.Methods and analysisThree databases will be searched (PubMed, EMBASE, CINAHL) from inception to March 2020. Reference lists, citations and grey literature will also be searched. Inclusion criteria are: (1) prospective cohort studies; (2) investigations of two key exposures: (a) lifestyle factor combinations of at least three lifestyle factors (eg, smoking, physical activity and diet) and (b) SES (eg, income, education or poverty index); (3) an assessment of the impact of SES on the association between combinations of unhealthy lifestyle factors and health outcomes; (4) at least one outcome from—mortality (all cause, CVD and cancer), CVD or cancer incidence. Two independent reviewers will screen titles, abstracts and full texts of included studies. Data extraction will focus on cohort characteristics, exposures, direction and magnitude of SES effects, methods and quality (via Newcastle-Ottawa Scale). If appropriate, a meta-analysis, pooling the effects of SES, will be performed. Alternatively, a synthesis without meta-analysis will be conducted.Ethics and disseminationEthical approval is not required. Results will be disseminated via peer-reviewed publication, professional networks, social media and conference presentations.PROSPERO registration numberCRD42020172588.

scholarly journals Self-Reported Energy Trajectories Predict Adverse Health Outcomes in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 794-795
Author(s):  
Briana Sprague ◽  
Xiaonan Zhu ◽  
Rebecca Ehrenkranz ◽  
Qu Tian ◽  
Theresa Gmelin ◽  
...  
Keyword(s):  
Older Adults ◽  
Health Outcomes ◽  
Mixed Models ◽  
Single Item ◽  
Adverse Health ◽  
Adverse Health Outcomes ◽  
Observational Cohort ◽  
Outcome Performance ◽  
Future Work ◽  
Mortality Hazard Ratio

Abstract Declining energy may indicate homeostatic dysregulation and predict adverse health outcomes. We hypothesized that declining energy would predict greater frailty (1-10), greater mortality, and faster mood (CES-D) and cognition (3MS) decline over time. This observational cohort studies included 2,443 older adults (mean age=74.6, 62.5% White, 47.8% men) from the Health ABC Study with up to eight years of data. Energy was assessed using a single-item question about prior month’s energy (baseline mean=6.7, SD=1.7, range=0–10, lower=less energy). We used linear mixed models to create energy change scores (mean=-.07 points/year, SD=.05, range=-0.32-0.21, negative=decreased energy). In regression models adjusting for baseline outcome performance and energy and demographics, declining energy predicted greater frailty (β=-2.72, 95%CI = -3.39,-2.06), greater mortality (hazard ratio=.07, p<.001), and faster CES-D (β=-.93, 95%CI=-1.10,-0.75) but not 3MS decline. Energy changes are easy to assess and predict clinically-relevant outcomes. Future work should consider mechanisms of declining energy on disability-related outcomes. Part of a symposium sponsored by Brain Interest Group.

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