Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity

Geeta D. Thakker, Nikolaos G. Frangogiannis, Pawel T. Zymek, Saumya Sharma, Joe L. Raya, Philip M. Barger, Heinrich Taegtmeyer, Mark L. Entman, Christie M. Ballantyne

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity.

Original languageEnglish (US)
Pages (from-to)2593-2600
Number of pages8
JournalObesity
Volume16
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

Fingerprint

Obese Mice
High Fat Diet
Ischemia
Reperfusion
Obesity
Diet
Fatty Acids
Cardiomyopathies
Nonesterified Fatty Acids
Enzyme Induction
Wounds and Injuries
Inbred C57BL Mouse
Genes
Histology
Triglycerides
Cardiovascular Diseases
Down-Regulation
Anesthesia
Antioxidants
Calcium

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Thakker, G. D., Frangogiannis, N. G., Zymek, P. T., Sharma, S., Raya, J. L., Barger, P. M., ... Ballantyne, C. M. (2008). Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity. Obesity, 16(12), 2593-2600. https://doi.org/10.1038/oby.2008.414

Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity. / Thakker, Geeta D.; Frangogiannis, Nikolaos G.; Zymek, Pawel T.; Sharma, Saumya; Raya, Joe L.; Barger, Philip M.; Taegtmeyer, Heinrich; Entman, Mark L.; Ballantyne, Christie M.

In: Obesity, Vol. 16, No. 12, 12.2008, p. 2593-2600.

Research output: Contribution to journalArticle

Thakker, GD, Frangogiannis, NG, Zymek, PT, Sharma, S, Raya, JL, Barger, PM, Taegtmeyer, H, Entman, ML & Ballantyne, CM 2008, 'Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity', Obesity, vol. 16, no. 12, pp. 2593-2600. https://doi.org/10.1038/oby.2008.414
Thakker, Geeta D. ; Frangogiannis, Nikolaos G. ; Zymek, Pawel T. ; Sharma, Saumya ; Raya, Joe L. ; Barger, Philip M. ; Taegtmeyer, Heinrich ; Entman, Mark L. ; Ballantyne, Christie M. / Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity. In: Obesity. 2008 ; Vol. 16, No. 12. pp. 2593-2600.
@article{1ecdc9a4c0b945a0913b8a58ef2abf9b,
title = "Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity",
abstract = "Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity.",
author = "Thakker, {Geeta D.} and Frangogiannis, {Nikolaos G.} and Zymek, {Pawel T.} and Saumya Sharma and Raya, {Joe L.} and Barger, {Philip M.} and Heinrich Taegtmeyer and Entman, {Mark L.} and Ballantyne, {Christie M.}",
year = "2008",
month = "12",
doi = "10.1038/oby.2008.414",
language = "English (US)",
volume = "16",
pages = "2593--2600",
journal = "Obesity",
issn = "1930-7381",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity

AU - Thakker, Geeta D.

AU - Frangogiannis, Nikolaos G.

AU - Zymek, Pawel T.

AU - Sharma, Saumya

AU - Raya, Joe L.

AU - Barger, Philip M.

AU - Taegtmeyer, Heinrich

AU - Entman, Mark L.

AU - Ballantyne, Christie M.

PY - 2008/12

Y1 - 2008/12

N2 - Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity.

AB - Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity.

UR - http://www.scopus.com/inward/record.url?scp=58149303032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149303032&partnerID=8YFLogxK

U2 - 10.1038/oby.2008.414

DO - 10.1038/oby.2008.414

M3 - Article

VL - 16

SP - 2593

EP - 2600

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 12

ER -