Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism

Daniel J. Sassoon, Adam G. Goodwill, Jillian N. Noblet, Abass M. Conteh, B. Herring, Jeanette McClintick, Johnathan Tune, Kieren Mather

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion.

Original languageEnglish (US)
Article number43
JournalBasic Research in Cardiology
Volume111
Issue number4
DOIs
StatePublished - Jul 1 2016

Fingerprint

Reperfusion
Ischemia
Obesity
Swine
Blood Pressure
Connectin
Glucagon-Like Peptide 1
Troponin I
Glucagon-Like Peptide-1 Receptor
Hypertriglyceridemia
Coronary Occlusion
Hyperinsulinism
Proteome
MicroRNAs
Transcriptome
Histidine
Hyperglycemia
Stroke Volume
Carrier Proteins
Fats

Keywords

  • Cardiovascular
  • Exendin-4
  • GLP-1
  • Ischemia
  • MicroRNA
  • Obesity
  • Proteomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism. / Sassoon, Daniel J.; Goodwill, Adam G.; Noblet, Jillian N.; Conteh, Abass M.; Herring, B.; McClintick, Jeanette; Tune, Johnathan; Mather, Kieren.

In: Basic Research in Cardiology, Vol. 111, No. 4, 43, 01.07.2016.

Research output: Contribution to journalArticle

Sassoon, Daniel J. ; Goodwill, Adam G. ; Noblet, Jillian N. ; Conteh, Abass M. ; Herring, B. ; McClintick, Jeanette ; Tune, Johnathan ; Mather, Kieren. / Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism. In: Basic Research in Cardiology. 2016 ; Vol. 111, No. 4.
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