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

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
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1097/01.hjh.0000203846.34314.94

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • High-fat feeding that is associated with the development of insulin resistance and obesity is associated with development of LV dysfunction in many but not all studies.

    “In contrast, high-fat feeding that is associated with the development of insulin resistance and obesity is associated with development of LV dysfunction in many (269, 273, 296) but not all studies (40).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [296]

  • A high-fat diet-induced hyperinsulinemic and insulin-resistant rat model of obesity did not detect significant differences in apoptosis despite impaired cardiomyocyte function.

    “Another very recent study used the high-fat diet-induced hyperinsulinemic and insulin-resistant rat model of obesity and did not detect significant differences in apoptosis despite impaired cardiomyocyte function (296).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [296]

Cites

Flagged first, then by citations

1 of the 56 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review