PP180. Maternal plasma endotoxin increases significantly across pregnancy with no association with obesity, inflammation, or insulin sensitivity

Powers, Robert W.; Kotchey, Nicole Marie; Gandley, Robin E.; Jeyabalan, Arundhathi; Hubel, Carl A.

doi:10.1016/j.preghy.2012.04.291

Cited by 2 publications

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“…Although ME has been characterized in nonpregnant women, few studies focus on its importance to the mother and the fetus in pregnancy. 18 29 30 Given insights from the DOHaD hypothesis, individuals exposed in utero to ME may be at risk of development of metabolic perturbations later in life. However, consideration must be given to what markers of ME are able to cross the placenta from maternal to fetal circulation, and what markers may be arising from the placental or fetal response.…”

Section: Discussionmentioning

confidence: 99%

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain

et al. 2021

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Objective Obesity in pregnancy bears unique maternal and fetal risks. Obesity has also been associated with chronic inflammation, including elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher serum lipopolysaccharide (LPS) levels have been implicated in driving this inflammation, a phenomenon called metabolic endotoxemia (ME). GLP-2, a proglucagon-derived peptide, is believed to be integral in maintaining the integrity of the intestine in the face of LPS-mediated endotoxemia. We hypothesized that obesity and/or excess weight gain in pregnancy would be associated with an increase in maternal and neonatal markers of ME, as well as GLP-2. Study Design Paired maternal and neonatal (cord blood) serum samples (n = 159) were obtained from our pregnancy biobank repository. Serum levels of LPS, endotoxin core antibody-immunoglobulin M (EndoCAb-IgM), and GLP-2 were measured by ELISA. IL-6 and TNF-α were measured using a Milliplex assay. Results were stratified by maternal body mass index (BMI), maternal diabetes, and gestational weight gain (GWG). Results Maternal IL-6 is significantly decreased in the obese, diabetic cohort compared with the nonobese, nondiabetic cohorts (95.28 vs. 99.48 pg/mL, p = 0.047), whereas GLP-2 is significantly increased (1.92 vs. 2.89 ng/mL, p = 0.026). Neonatal TNF-α is significantly decreased in the obese cohort compared with the nonobese cohort (12.43 vs. 13.93 pg/mL, p = 0.044). Maternal GLP-2 is significantly increased in women with excess GWG compared with those with normal GWG (2.27 vs. 1.48 ng/mL, p = 0.014). We further found that neonatal IL-6 and TNF-α are negatively correlated with maternal BMI (−0.186, p = 0.036 and –0.179, p = 0.044, respectively) and that maternal and neonatal IL-6 showed a positive correlation (0.348, p < 0.001). Conclusion Although we observed altered levels of markers of inflammation (IL-6 and TNF-α) with maternal obesity and diabetes, no changes in LPS or endoCAb-IgM were observed. We hypothesize that the increased GLP-2 levels in maternal serum in association with excess GWG may protect against ME in pregnancy. Key Points

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Section: Discussionmentioning

confidence: 99%

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain

et al. 2021

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Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice

et al. 2020

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23Maternal obesity is one of the major risk factors for pregnancy complications and is associated with 24 low-grade chronic systemic inflammation due to higher levels of pro-inflammatory cytokines such 25 as interleukin (IL)-1β. Pregnant women with obesity have abnormal lipid profiles, characterized by 26 higher levels of free fatty acids, especially palmitic acid (PA). Previously, we reported that PA 27 stimulated IL-1β secretion via activation of NLRP3 inflammasome in human placental cells. These 28 observations led us to hypothesize that higher levels of PA induce NLRP3 inflammasome activation 29 and placental inflammation, resulting in pregnancy complications. However, the effects of PA on 30 NLRP3 inflammasome during pregnancy in vivo remain unclear. Therefore, PA solutions were 31 administered intravenously into pregnant mice on day 12 of gestation. Maternal body weight was 32 significantly decreased and absorption rates were significantly higher in PA-injected mice. The 33 administration of PA significantly increased IL-1β protein and the mRNA expression of NLRP3 34 inflammasome components (NLRP3, ASC, and caspase-1) within the placenta. In murine placental 35 cell culture, PA significantly stimulated IL-1β secretion, and this secretion was suppressed by a 36 specific NLRP3 inhibitor (MCC950). Simultaneously, the number of macrophages/monocytes and 37 neutrophils, together with the mRNA expression of these chemokines increased significantly in the 38 placentas of PA-treated mice. Treatment with PA induced ASC assembling and IL-1β secretion in 39 macrophages, and this PA-induced IL-1β secretion was significantly suppressed in NLRP3-knockout 40 macrophages. These results indicate that transient higher levels of PA exposure in pregnant mice 41 activates NLRP3 inflammasome and induces placental inflammation, resulting in the incidence of 42 absorption. 43 44 48 is a low-grade chronic systemic inflammation and associated with insulin resistance, cardiovascular 49 diseases, and diabetes [3]. Pregnant women with obesity are associated with elevated serum levels of 50 pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α, 51compared to pregnant women with normal weight [4][5][6][7]. Pregnant women with obesity have 52 abnormal lipid profiles, characterized by higher levels of free fatty acids (FFAs) [8, 9]. It has been 53 reported that palmitic acid (PA), the most abundant saturated FFAs in the blood, promotes 54 inflammatory responses by directly engaging toll-like receptors (TLR), and inducing nuclear factor-55 κB (NF-κB)-dependent production of inflammatory cytokines [10, 11]. Previously, we reported that 56 PA caused inflammatory cytokine secretion, inducing IL-1β, IL-6, and IL-8 in human placental cells 57 [12], suggesting that obesity-related PA accumulation induces placental inflammation. 58Recently, there have been numerous reports of inflammasome mechanisms that control 59 sterile inflammation involved in pregnancy pathologies [13][14][15][16]. Inflammasomes are l...

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PP180. Maternal plasma endotoxin increases significantly across pregnancy with no association with obesity, inflammation, or insulin sensitivity

Cited by 2 publications

References 0 publications

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain

Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice

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