Cited by 151Cardiovascular Function and Risk FactorsCardiac electrophysiology and arrhythmiasCardiac Fibrosis and Remodeling

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High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis

Relling, David P, Esberg, Lucy B, Fang, Cindy X, Johnson, W Thomas, Murphy, Eric J, Carlson, Edward C, Saari, Jack T, Ren, Jun·2006·Journal of Hypertension

DOI 10.1097/01.hjh.0000203846.34314.94

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Abstract

BACKGROUND: Obesity is associated with dyslipidemia, which leads to elevated triglyceride and ceramide levels, apoptosis and compromised cardiac function. METHODS: To determine the role of high-fat diet-induced obesity on cardiomyocyte function, weanling male Sprague-Dawley rats were fed diets incorporating 10% of kcal or 45% of kcal from fat. Mechanical function of ventricular myocytes was evaluated including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening and relengthening (+/- dl/dt). Intracellular Ca properties were assessed using fluorescent microscopy. RESULTS: High-fat diet induced hyperinsulinemic insulin-resistant obesity with depressed PS, +/- dl/dt, prolonged TPS/TR90 reduced intracellular Ca release and Ca clearing rate in the absence of hypertension, diabetes, lipotoxicity and apoptosis. Myocyte responsiveness to increased stimulus frequency and extracellular Ca was compromised. SERCA2a and phospholamban levels were increased, whereas phosphorylated phospholamban and potassium channel (Kv1,2) were reduced in high-fat diet group. High-fat diet upregulated the forkhead transcription factor Foxo3a, and suppressed mitochondrial aconitase activity without affecting expression of the caloric sensitive gene silent information regulator 2 (Sir2), protein nitrotyrosine formation, lipid peroxidation and apoptosis. Levels of endothelial nitric oxide synthase (NOS), inducible NOS, triglycerides and ceramide were similar between the two groups. CONCLUSIONS: Collectively, our data show that high-fat diet-induced obesity resulted in impaired cardiomyocyte function, upregulated Foxo3a transcription factor and mitochondrial damage without overt lipotoxicity or apoptosis.

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Authors: Relling, D. P., Esberg, L. B., Fang, C. X., Johnson, W. T., Murphy, E. J., Carlson, E. C., Saari, J. T., & Ren, J.
Affiliations: University of North Dakota (US)
University of Wyoming (US)
Agricultural Research Service (US)
Corresponding author: Ren, Jun
ORCID: Johnson, W Thomas
Murphy, Eric J
Ren, Jun
Venue: Journal of Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2006-03
Volume: 24
Issue: 3
Pages: 549-561
ISSN: 0263-6352 (ISSN-L)
DOI: 10.1097/01.hjh.0000203846.34314.94
OpenAlex: W1979714251
Cited by: 151
References: 56
Citations by year: 2024: 5 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 10 · 2019: 2 · 2018: 5 · 2017: 9 · 2016: 9 · 2015: 6 · 2014: 12 · 2013: 10 · 2012: 9
FWCI: 7.35
Type: journal article
Language: en
Open access: closed
Locations: Journal of Hypertension (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Agriculture
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords: high-fat diet, youth obesity, cardiomyocyte dysfunction, FOXO3, mitochondrial aconitase, intracellular calcium homeostasis, SERCA2a, phospholamban, Kv1.2 potassium channel, insulin resistance, dyslipidemia, ceramide, triglycerides, mitochondrial damage, cardiac contractility
MeSH terms: Forkhead Box Protein O3, Phospholamban, Aconitate Hydratase, Calcium-Transporting ATPases, Animals, Calcium, Calcium-Binding Proteins, Ceramides, Dietary Fats, Male, Obesity, Sarcoplasmic Reticulum, Triglycerides, Tyrosine, Up-Regulation, Rats, Sprague-Dawley, Apoptosis, Nitric Oxide Synthase, Potassium Channels, Voltage-Gated, Myocytes, Cardiac, Sirtuins, STAT3 Transcription Factor, Rats, Forkhead Transcription Factors, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Sirtuin 1, In Vitro Techniques

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High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis

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