Cardiac Effects of Obesity During Pregnancy in C57BL/6J Mice
Authors: Dudick Kayla L. , Che Chen , Shoemaker Robin C. 
Published: April 2020

ObjectivePregnancy requires profound cardiac and metabolic adaptation. Left ventricular (LV) mass is increased in response to pregnancy, but is not associated with cardiac damage. In contrast, obesity‐mediated cardiac hypertrophy is pathological. Over a third of reproductive‐age women in the United States are obese, but there is a paucity of data describing the effect of obesity on maternal cardiac adaptation to pregnancy. The objective of this study was to determine the effects of high‐fat feeding during pregnancy on cardiac function and structure in a mouse model of diet‐induced obesity.Methods/ResultsFemale C57BL/6J mice (8 weeks old) were fed a high fat (HF; 60% kcal from fat) or a control low fat (LF; 10% kcal from fat) diet for 8 weeks, then were either crossed with male mice to become pregnant (P) or remained non‐pregnant (NP) controls. At gestational day 18, cardiac function was quantified by echocardiography in LF‐ and HF‐fed P and NP females. On gestational 19 day, mice were euthanized for tissue collection. HF‐fed females had significantly increased body weight compared to LF‐fed controls (P<0.001), and body weight was increased in P compared to NP mice (P<0.001; LF NP: 22.3 ± 0.8 [n=20], LF P: 34.8 ± 1.3 [n=10], HF NP: 32.7 ± 0.9 [n=18], HF P: 39.2 ± 1.1 [n=12] g). In response to pregnancy, LF‐, but not HF‐fed, mice had significantly increased LV mass (LF NP: 60.0 ± 2.4, LF P: 75.5 ± 3.1, HF NP: 70.3 ± 2.0, HF P: 75.1 ± 3.8 mg; P<0.01), LV end‐diastolic diameter (LF NP: 3.60 ± 0.05, LF P: 3.95 ± 0.07, HF NP: 3.67 ± 0.05, HF P: 3.73 ± 0.01 mm; P<0.01), and cardiac output (CO; LF NP: 11.7 ± 0.7, LF P: 13.9 ± 0.7, HF NP: 11.4 ± 0.4, HF P: 12.9 ± 0.7 mL/min; P<0.05) compared to NP controls. In contrast, HF‐fed pregnant mice had increased relative wall thickness (RWT; LF NP: 0.36 ± 0.01, LF P: 0.35 ± 0.01, HF NP: 0.39 ± 0.01, HF P: 0.40 ± 0.02 [2* LV posterior wall thickness/LV end‐diastolic diameter], P<0.05) and ejection fraction (EF; LF NP: 52.5 ± 2.6, LF P: 54.7 ± 2.7, HF NP: 50.7 ± 2.0, HF P: 60.8 ± 2.5 %, P<0.05) compared to LF‐fed pregnant mice. We quantified mRNA abundance of genes regulating fatty acid oxidation (FAO) and glycolysis in left ventricles of LF‐ and HF‐fed pregnant and non‐pregnant mice using Nanostring nCounter Analysis system. Preliminary results indicate that pregnancy and HF‐feeding were independently associated with increased expression of genes regulating FAO, such as carnitine palmitoyl transferase‐1b (LF NP: 3369 ± 89, LF P: 3964 ± 193. HF NP: 4133 ± 154, HF P: 4551 ± 257 mRNA counts). However, the effect was not significantly augmented in HF‐fed pregnant mice. In contrast, genes regulating glycolysis, such as hexokinase‐2, were decreased with pregnancy (LF NP: 83 ± 5, LF P: 60 ± 5. HF NP: 71 ± 4, HF P: 72 ± 7 mRNA counts), consistent with literature, but this effect was only observed in LF‐fed mice.ConclusionsCardiac hypertrophy in response to pregnancy was observed in LF‐fed, but not HF‐fed mice. In contrast, HF‐fed pregnant mice had increased RWT and decreased LV end‐diastolic diameter compared to LF‐fed pregnant mice. This was accompanied by increased EF and alterations in expression of genes regulating cardiac metabolism compared to LF‐fed pregnant mice. Taken together, these data suggest that obesity during pregnancy increases cardio‐metabolic demand and work, and may be associated with aberrant cardiac metabolism.Support or Funding InformationSupported by NIH P30 GM127211 and NIGMS 3210001211