Author ORCID Identifier

https://orcid.org/0000-0001-6583-192X

Date Available

11-19-2020

Year of Publication

2020

Document Type

Master's Thesis

Degree Name

Master of Science in Nutrition and Food Systems (MSNFS)

College

Agriculture, Food and Environment

Department/School/Program

Dietetics and Human Nutrition

Advisor

Dr. Robin Shoemaker

Abstract

Objective: Pregnancy 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. Data from animal studies indicate dietary fatty acid composition may have a protective effect during states of extreme cardiac physiological adaptation. In contrast, aberrant cardiac metabolism is a hallmark of disease. 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 hypertrophy and metabolism in a mouse model of diet-induced obesity.

Methods/Results:Female 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, and body weight was increased in P compared to NP mice. In response to pregnancy, LF-, but not HF-fed, mice had significantly increased LV mass (P Acaa2, Acox1,and Acadl (genes regulated long-chain fatty acid oxidation) and Cpt1b (regulating fatty acid transport into the mitochondria) were upregulated with both HF-feeding and pregnancy. In contrast, Ehhadh, a gene regulating production of medium chain fatty acids during fatty acid oxidation, was increased in pregnant mice, but only in the LF mice, and the expression was significantly reduced in HF- compared to LF-fed pregnant mice.

Conclusions: Physiological cardiac hypertrophy in response to pregnancy was observed in LF-fed, but not HF-fed mice. In contrast, HF-fed pregnant mice had increased RWT compared to LF-fed pregnant mice. While fatty acid utilization was increased with HF-feeding and pregnancy, the expression of Ehhadh was reduced in HF- compared to LF-fed mice. Medium chain fatty acids are demonstrated in the literature to be protective against pathological cardiac remodeling in experimental animals. Taken together, these data suggest obesity may impair protective fatty acid utilization pathways in pregnancy to promote adverse cardiac remodeling.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2020.431

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