Abstract
Dietary fats are essential for cardiac function. The metabolites of fats known as fatty acids provide most of the energy for cardiac tissue, serve as building blocks for membranes and regulate important signaling cascades. Despite their importance, excess fat intake can cause cardiac dysfunction. The detrimental effects of high‐fat diet (HFD) on cardiac health are widely investigated in long‐term studies but the short‐term effects of fats have not been thoroughly studied. To elucidate the near‐term effects of a HFD on the growth and maturation of late adolescent heart we subjected 11‐week‐old mice to an 8‐week long HFD (42% of calories from fat, 42% from carbohydrate, n = 8) or chow diet (12% of calories from fat, 66% from carbohydrate, n = 7) and assessed their effects on the heart in vivo and in vitro. Our results showed that excessive fat feeding interferes with normal maturation of the heart indicated by the lack of increase in dimensions, volume, and stroke volume of the left ventricles of mice on high fat diet that were evident in mice on chow diet. In addition, differences in regional strain during the contraction cycle between mice on HFD and chow diet were seen. These changes were associated with reduced activity of the growth promoting PI3K‐Akt1 signaling cascade and moderate changes in glucose metabolism without changes in calcium signaling. This study suggests that even a short period of HFD during late adolescence hinders cardiac maturation and causes physiological changes that may have an impact on the cardiac health in adulthood.
Highlights
Fatty acids (FAs), the metabolites of dietary fats, are used for energy, cell and organelle membrane building, and signaling pathway regulation throughout the body
This study demonstrates that an 8-week long high-fat diet (HFD) started at 11weeks of age hindered the normal physiological maturation of the heart
At the cellular level these changes were associated with changes in glucose metabolism and reduced activity of PI3K-Akt1 signaling cascade
Summary
Fatty acids (FAs), the metabolites of dietary fats, are used for energy, cell and organelle membrane building, and signaling pathway regulation throughout the body. Adolescent obesity is a predisposing factor to cardiac pathologies later in life as recent extensive long-term follow-up studies show that high body mass index in late adolescence increases the risk of cardiomyopathy, hypertension, arrhythmias, arterial disease, and heart failure alongside with increased mortality associated with these diseases in adulthood in humans (Robertson et al, 2019; Twig et al, 2017). In mice long-term high-fat diet (HFD) consumed in juvenility induces contractile dysfunction and hypertrophy, as well as functional and structural changes in the heart resembling those seen in diabetic cardiomyopathy (Abdurrachim et al, 2014; Calligaris et al, 2013; Fang et al, 2008; Wang, Li, Zhao, Peng, & Zuo, 2015; Zeng, Vaka, He, Booz, & Chen, 2015). It is evident that deviations from normal conditions, for example obesity and excessive dietary fat intake can interfere with the final maturation steps of the heart. Cellular level changes were elucidated by examining energy metabolism, as well as calcium and growth signaling pathways in vitro
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