Maternal Exercise Intervention in Obese Pregnancy Improves the Cardiovascular Health of the Adult Male Offspring


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Authors
Beeson, JH 
Blackmore, Heather 
Carr, Sarah 
Duque-Guimarães, Daniella 
Abstract

OBJECTIVE Obesity during pregnancy is associated with an elevated risk of cardiovascular disease in the offspring. With increased numbers of women entering pregnancy overweight or obese, there is a requirement for targeted interventions to reduce disease risk in future generations. Using an established murine model of maternal obesity during pregnancy, we investigated if a treadmill exercise intervention in the mother could improve offspring cardiac health and explored potential underlying mechanisms. METHODS A 20-minute treadmill exercise intervention protocol was performed 5 days a week in diet-induced obese female C57BL/6 mice 1 week prior to, and up to E17 of pregnancy. All male offspring were weaned onto a control diet and studied at 8 weeks of age when their cardiovascular physiology was assessed by in vivo echocardiography and non-invasive tail cuff plethysmography. Cardiomyocyte cell area, re-expression of fetal genes and the expression of calcium handling and sympathetic activation proteins were determined. RESULTS At 8 weeks, there was no difference in bodyweight or fat mass between groups. Offspring of obese dams developed pathologic cardiac hypertrophy, hypertension and cardiac dysfunction characterized by reduced ejection fraction (p< 0.001). Maternal exercise prevented cardiac hypertrophy and dysfunction but failed to prevent hypertension. These offspring of exercised dams also had enhanced (p< 0.001) levels of calcium handling proteins and a sympathetic-activated inotropic response. CONCLUSIONS Exercise in obese pregnancy was beneficial to offspring cardiac function and structure but did not influence hypertension suggesting they are programmed by separate mechanistic pathways. These data suggest combination interventions in obese pregnancies will be required to improve all aspects of the cardiovascular health of the next generation.

Description
Keywords
Echocardiography, Exercise, Hypertrophy, Obesity, Pregnancy, Adiposity, Animals, Body Composition, Body Weight, Cardiovascular Physiological Phenomena, Diet, Exercise Therapy, Female, Lactation, Male, Mice, Mice, Inbred C57BL, Obesity, Overweight, Physical Conditioning, Animal, Physical Exertion, Pregnancy, Pregnancy Complications, Prenatal Care, Weaning
Journal Title
Molecular Metabolism
Conference Name
Journal ISSN
2212-8778
2212-8778
Volume Title
16
Publisher
Elsevier
Sponsorship
British Heart Foundation (RG/17/12/33167)
British Heart Foundation (None)
European Commission (289346)
Medical Research Council (MC_UU_12012/4)
British Heart Foundation (None)
Wellcome Trust (106026/Z/14/Z)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
Isaac Newton Trust (MINUTE 544(I))
Lister Institute of Preventive Medicine (unknown)
MRC (unknown)
Wellcome Trust (072256/Z/03/Z)
Sir Jules Thorn Charitable Trust (05SC/06A)
Biotechnology and Biological Sciences Research Council (BB/E002668/1)
British Heart Foundation (None)
The Royal Society (wm062239)
Wellcome Trust (VS/06/CAM/A15)
Isaac Newton Trust (1238(S))
British Heart Foundation (None)
British Heart Foundation (None)
Wellcome Trust (072256/Z/03/A)
Wellcome Trust (089941/Z/09/A)
Action Medical Research (via Imperial College London) (WS/ 3074260)
Lister Institute of Preventive Medicine (unknown)
Lister Institute of Preventive Medicine (unknown)
Genesis Research Trust (via Imperial College London) (WS/3381326)
Lister Institute of Preventive Medicine (unknown)
British Heart Foundation (RG/17/8/32924)
Lister Institute of Preventive Medicine (unknown)
British Heart Foundation (None)
MRC (MC_UU_00014/4)
This work received funding from the British Heart Foundation, the European Union’s Seventh Framework Programme , MRC Metabolic Diseases Unit award and British Heart Foundation Studentship. Wellcome Trust.