Maternal diet-induced obesity programs cardiovascular dysfunction in adult male mouse offspring independent of current body weight.

Change log
Blackmore, Heather L 
Niu, Youguo 
Fernandez-Twinn, Denise S 
Tarry-Adkins, Jane L 
Giussani, Dino A 

Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet-induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.

Animals, Body Weight, Cardiovascular Diseases, Cells, Cultured, Diet, Embryonic Development, Female, Maternal Nutritional Physiological Phenomena, Mice, Mice, Inbred C57BL, Obesity, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects
Journal Title
Conference Name
Journal ISSN
Volume Title
The Endocrine Society
Biotechnology and Biological Sciences Research Council (BB/E002668/1)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/4)
Medical Research Council (G0600717)
Medical Research Council (MC_UU_12012/5)
HLB, YN and JLTA are funded by the British Heart Foundation. DFT is supported by the MRC Metabolic Diseases Unit. DAG is a Lister Institute Fellow and Royal Society Wolfson Merit Award Holder and is supported by the British Heart Foundation. SEO is a British Heart Foundation Senior Fellow and a member of the MRC Metabolic Diseases Unit.