Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Aye, Irving L.M.H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

doi:10.1073/pnas.1515484112

Cited by 137 publications

(146 citation statements)

References 44 publications

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“…Adiponectin is an adipocyte-derived hormone that has been suggested to mediate maternal obesity-altered fetal growth [23, 44]. Recent studies, including our work, demonstrated that adiponectin is not expressed in the placenta and cannot pass through the placental barrier [23, 33].…”

Section: Discussionmentioning

confidence: 73%

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

et al. 2016

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Aims/hypothesis The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Methods Adiponectin knockout (Adipoq−/−) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. Results The body weight of fetuses from Adipoq−/− dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq−/− dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq−/− and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq−/− dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq−/− dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. Conclusions/interpretation These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.

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Section: Discussionmentioning

confidence: 73%

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

et al. 2016

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“…1). Drivers associated with maternal insulin resistance might include excess fuel supply, inflammation, hormones (for example adiponectin 44 ) and fetal hypoxia, as discussed later. In humans, increased maternal insulin resistance, independent of excessive gestational weight gain, mediates fetal adiposity 45 , and increased maternal insulin resistance in mice results in progressive development of postnatal lipid deposition in the offspring 46 .…”

Section: Intrauterine Clues For Nafld Riskmentioning

confidence: 99%

Developmental origins of NAFLD: a womb with a clue

Wesolowski

Kasmi

Jonscher

et al. 2016

Nat Rev Gastroenterol Hepatol

179

167

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Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation.NAFLD is a general term used to describe a broad spectrum of liver abnormalities, ranging from simple, uncomplicated hepatic steatosis to NASH, accompanied by different degrees of Correspondence to J.E.F. jed.friedman@ucdenver.edu. Author contributionsAll authors researched data for the article, provided a substantial contribution to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Gastroenterol Hepatol. Author manuscript; available in PMC 2017 December 12. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript inflammation and fibrosis. NAFLD is increasing in prevalence, especially in adolescents 1 , despite the levellingoff of the obesity epidemic from 2003-2004 to 2013-2014 in children and adolescents aged 2-19 years (REF.2). The most common chronic liver disease worldwide, NAFLD increases the risk of cardiovascular events eightfold and type 2 diabetes mellitus (T2DM) threefold 3 , and is a strong risk factor for hepatocellular carcinoma (HCC) 4 . At the time of paediatric NAFLD diagnosis, 25-50% of children have NASH and 10-25% have advanced fibrosis 5 . For many decades, it was thought that NAFLD was predominantly driven by obesity in the setting of genetic suscep...

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“…These aspects include insulin and adipokines, such as leptin and 195 adiponectin as well as cytokines [62,63] and placental nutrient sensing pathways [65]. 202…”

Section: Maternal Overweight and Obesity 192 193mentioning

confidence: 99%

Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes

2017

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Please cite this article as: Gallo LA, Barrett HL, Nitert MD, Placental transport and metabolism of energy substrates in maternal obesity and diabetes, Placenta (2017), doi: 10.1016/j.placenta.2016.12.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Cited by 137 publications

References 44 publications

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

Developmental origins of NAFLD: a womb with a clue

Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes

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