PMID- 31076636 OWN - NLM STAT- MEDLINE DCOM- 20210226 LR - 20210731 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 44 IP - 2 DP - 2020 Feb TI - Normalisation of circulating adiponectin levels in obese pregnant mice prevents cardiac dysfunction in adult offspring. PG - 488-499 LID - 10.1038/s41366-019-0374-4 [doi] AB - BACKGROUND/OBJECTIVES: Adiponectin concentrations are low in obese pregnant women. Restoring normal adiponectin concentrations by infusion in obese pregnant mice prevents placental dysfunction, foetal overgrowth and metabolic syndrome in the offspring. We hypothesised that normalising maternal adiponectin in obese late pregnant dams prevents cardiac dysfunction in the adult offspring. SUBJECTS/METHODS: Pregnant female mice with diet-induced obesity were infused with adiponectin (0.62 mug g(-1) day(-1), n = 24) or saline (n = 22) over days 14.5-18.5 of pregnancy (term = day 19.5). Control dams ate standard chow and received saline (n = 22). Offspring were studied at 3 and 6 months of age. RESULTS: Maternal obesity impaired ventricular diastolic function, increased cardiomyocyte cross-sectional area and upregulated cardiac brain natriuretic peptide (Nppb) and alpha-skeletal actin (Acta1) gene expression in adult male offspring, compared to control offspring. In adult female offspring, maternal obesity increased Nppb expression, decreased end-diastolic volume and caused age-dependent diastolic dysfunction but not cardiomyocyte hypertrophy. Maternal obesity also activated cardiac Akt and mechanistic target of rapamycin (mTOR) signalling in male, but not in female, offspring and inhibited cardiac extracellular signal-regulated kinase 1/2 (ERK1/2) in both sexes. Normalising maternal circulating adiponectin concentrations by infusing obese dams with adiponectin prevented offspring diastolic dysfunction and ventricular dilation and normalised cardiac Akt-mTOR signalling irrespective of sex. Maternal adiponectin infusion also reduced cardiac Nppb expression and increased ERK1/2 signalling in offspring of obese dams. Adiponectin infusion did not prevent cardiomyocyte hypertrophy but reduced ventricular wall thickness in male offspring and increased collagen content in female offspring of obese dams, compared to controls. CONCLUSIONS: Low maternal adiponectin levels in obese mice in late pregnancy are mechanistically linked to in utero programming of cardiac dysfunction in their offspring. Interventions enhancing endogenous adiponectin secretion or signalling in obese pregnant women could prevent the development of cardiac dysfunction in their children. FAU - Vaughan, Owen R AU - Vaughan OR AUID- ORCID: 0000-0001-7537-3264 AD - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. owen.vaughan@ucdenver.edu. FAU - Rosario, Fredrick J AU - Rosario FJ AD - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Powell, Theresa L AU - Powell TL AD - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. AD - Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Jansson, Thomas AU - Jansson T AD - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. LA - eng GR - P30 DK048520/DK/NIDDK NIH HHS/United States GR - UL1 TR002535/TR/NCATS NIH HHS/United States GR - R01 HD065007/HD/NICHD NIH HHS/United States GR - S10 OD018156/OD/NIH HHS/United States GR - R24 OD016724/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190510 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Adiponectin) SB - IM MH - *Adiponectin/administration & dosage/blood/pharmacology MH - Animals MH - Echocardiography MH - Female MH - Heart/diagnostic imaging/physiopathology MH - Heart Diseases/*prevention & control MH - Male MH - Maternal Nutritional Physiological Phenomena/*drug effects MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Myocardium/pathology MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*prevention & control PMC - PMC6842414 MID - NIHMS1525654 COIS- The authors declare that they have no conflict of interest. EDAT- 2019/05/12 06:00 MHDA- 2021/02/27 06:00 PMCR- 2019/05/10 CRDT- 2019/05/12 06:00 PHST- 2018/10/31 00:00 [received] PHST- 2019/03/26 00:00 [accepted] PHST- 2019/03/06 00:00 [revised] PHST- 2019/05/12 06:00 [pubmed] PHST- 2021/02/27 06:00 [medline] PHST- 2019/05/12 06:00 [entrez] PHST- 2019/05/10 00:00 [pmc-release] AID - 10.1038/s41366-019-0374-4 [pii] AID - 374 [pii] AID - 10.1038/s41366-019-0374-4 [doi] PST - ppublish SO - Int J Obes (Lond). 2020 Feb;44(2):488-499. doi: 10.1038/s41366-019-0374-4. Epub 2019 May 10.