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Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages.

ABSTRACT: INTRODUCTION:There is an increasing prevalence of non-communicable diseases worldwide. Metabolic diseases such as obesity and gestational diabetes mellitus (GDM) increasingly affect women during pregnancy, which can harm pregnancy outcomes and the long-term health and wellbeing of exposed offspring. Both obesity and GDM have been associated with proinflammatory effects within the placenta, the critical organ governing fetal development. METHODS:The purpose of these studies was to model, in vitro, the effects of metabolic stress (high levels of glucose, insulin and saturated lipids) on placental macrophage biology, since these cells are the primary innate immune phagocyte within the placenta with roles in governing maternofetal immune tolerance and antimicrobial host defense. Macrophages were isolated from the villous core of term, human placentae delivered through nonlaboring, elective Cesarean sections and exposed to combinations of elevated glucose (30 mM), insulin (10 nM) and the saturated lipid palmitic acid (palmitate, 0.4 mM). RESULTS:We found that palmitate alone induced the activation of the nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in placental macrophages, which was associated with increased interleukin 1 beta release and an increase in apoptotic cell death. Glucose and insulin neither provoked these effects nor augmented the impact of palmitate itself. DISCUSSION:Our findings confirm an impact of saturated fat on placental macrophage immune activation and could be relevant to the impact of metabolic stress in vivo.

SUBMITTER: Rogers LM

PROVIDER: S-EPMC7034939 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages.

Rogers Lisa M LM Serezani Carlos H CH Eastman Alison J AJ Hasty Alyssa H AH Englund-Ögge Linda L Jacobsson Bo B Vickers Kasey C KC Aronoff David M DM

Placenta 20191209

<h4>Introduction</h4>There is an increasing prevalence of non-communicable diseases worldwide. Metabolic diseases such as obesity and gestational diabetes mellitus (GDM) increasingly affect women during pregnancy, which can harm pregnancy outcomes and the long-term health and wellbeing of exposed offspring. Both obesity and GDM have been associated with proinflammatory effects within the placenta, the critical organ governing fetal development.<h4>Methods</h4>The purpose of these studies was to ...[more]

PMID: 32056551

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Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages.

Publications

Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages.

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