Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease
Abstract
:1. Introduction
2. Pathobiology of Maternal Obesity
2.1. Maternal Systemic Low-Grade Inflammation
2.2. Placental Inflammation
2.3. Fetal Inflammation
3. Maternal Obesity-Related Inflammation and Developmental Programming
3.1. Evidence from Animal Models
3.2. Evidence from Human Studies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Animal Model | Inflammation Pathway | Offspring Outcomes | Maternal Outcomes | |
---|---|---|---|---|
Hara et al. (2000) [75] | Rodent/Human Pro12Ala PPARgamma2 polymorphism | Diet-induced |
↑ leptin |
↓ Ala12 in the diabetic group |
Nilsson et al. (2001) [76] | Rodent | LPS injection-induced |
↑ circulating leptin, 17beta-estradiol and progesterone ↑ hippocampal glucocorticoid receptor expression ↓ insulin sensitivity, corticosterone response to stress
heart and adrenals enlargement | |
Wei et al. (2007) [77] | Rodent | LPS injection-induced | ↑ systemic arterial blood pressure, body weight, food intake, adipose tissue weight ↑ circulating leptin | |
Perez-Echarri et al. (2008) [78] | Rodent | Diet-induced Eicosapentaenoic (EPA) omega-3 fatty acid treatment | ↑ TNF, IL-6 and haptoglobin in white adipose tissue ↓ haptoglobin serum levels
Reversal of serum haptoglobin increase; Prevention of obesity-associated inflammation in adipose tissue | |
Samuelsson et al. (2008) [79] | Rodent | Diet-induced | ↑ body weight, blood pressure, adiposity with adipocyte hypertrophy, hyperphagia; ↓ locomotor activity and skeletal muscle mass ↓ adipocyte β 2- and β 3-adrenoreceptor and PPAR-γ expression; Systemic artery endothelial dysfunction and hypertension ↑ fasting insulin and glucose levels | |
Gregorio et al. (2010) [80] | Rodent | Diet-induced | Liver modifications: Insulin resistance and lower GLUT-2 expression ↑ sterol regulatory element-binding protein-1c expression; Hepatic steatosis | |
Yan et al. (2010) [81] | Sheep | Diet-induced | Skeletal muscle modifications: ↑ PPAR-γ, TLR2–4, NF-κB, and TNFα gene expression ↑ intramuscolar adipogenesis and macrophage infiltration ↑ circulating insulin concentrations ↓ insulin receptor mRNA expression and insulin sensitivity | |
Park et al. (2010) [82] | Rodent | Diet-induced | ↑ tumor-promoting cytokines IL-6 and TNF which cause hepatic inflammation and activation of the oncogenic transcription factors → hepatocellular carcinoma development | |
Rattanatray et al. (2010) [83] | Sheep | Diet-induced | ↑ body fat mass in female offspring, reversible by maternal dietary restriction; No effect on PPAR-γ, G3PDH, lipoprotein lipase, leptin and adiponectin mRNA expression | |
Kirsten et al. (2013) [84] | Rodent | LPS injection-induced | ↑ IL-1β serum levels
| ↑ maternal serum corticosterone levels, higher postimplantation loss |
Murabayashi et al. (2013) [85] | Rodent | Diet-induced | = fetal weight ↑ plasma glucose and insulin levels adipocyte hypertrophy ↑ adipocyte expression of chemokine receptor-2 and TNFα mRNA ↓ adipocyte GLUT-4 expression | ↑ bodyweight, glucose intolerance and insulin resistance |
Desai et al. (2014) [86] | Rodent | Diet-induced (during pregnancy and/or lactation) | ↑ adiposity ↑ body weight only when overnutrition was prolonged during lactation; Hyperglycemia ↑ systolic blood pressure ↑ plasma corticosterone levels in case of maternal gestational overnutrition | ↑ body fat and plasma corticosterone levels |
Fink et al. (2014) [87] | Rodent Human | Diet-induced | Glucose intolerance
Dysregulated muscle inflammatory gene expression | |
Desai et al. (2016) [88] | Rodent | Diet-induced | ↑ adiposity despite unaffected body weight in males ↓ energy sensors (DNA methylase) ↑ appetite and ↓ satiety neuropeptides; Altered development, neuronal abnormal differentiation and appetite dysregulation in hypothalamus and adult arcuate nucleus | |
Thompson et al. (2016) [89] | Rodent | Diet-induced | ↑ hepatocyte proliferation and stellate cell activation; Hepatosteatosis ↑ susceptibility to development of steatosis and rapid disease progression with sustained fibrotic phenotype | |
Cadaret et al. (2018) [90] | Sheep | LPS injection-induced | Altered muscle metabolic capacity with ↓ glucose oxidation capacity FGR fetuses with –22% in body weight ↓ β cell function | ↑ circulating inflammatory cells |
Adams et al. (2019; 2020) [91,92] | Rodent (F1 and F2 generations) | LPS injection-induced | Glucocorticoid hypersensitivity in F1 offspring with elevated corticosterone and increased leukocyte glucocorticoid receptor level, further transmitted to the F2 offspring without additional insults (>male offspring) ↑ IL-1β cytokine responses in female offspring only | |
Litzenburger et al. (2020) [93] | Rodent | Diet-induced | ↑ white adipose tissue (female > male) ↑ adipocyte size Sex-dependent metabolic programming of white adipose tissue dysfunction with dysregulation of lipolytic, adipogenic and stemness-related markers |
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Parisi, F.; Milazzo, R.; Savasi, V.M.; Cetin, I. Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease. Int. J. Mol. Sci. 2021, 22, 1732. https://doi.org/10.3390/ijms22041732
Parisi F, Milazzo R, Savasi VM, Cetin I. Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease. International Journal of Molecular Sciences. 2021; 22(4):1732. https://doi.org/10.3390/ijms22041732
Chicago/Turabian StyleParisi, Francesca, Roberta Milazzo, Valeria M. Savasi, and Irene Cetin. 2021. "Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease" International Journal of Molecular Sciences 22, no. 4: 1732. https://doi.org/10.3390/ijms22041732