Cardioprotective Heme Oxygenase 1‐PGC1α Signaling in Epicardial Fat Attenuates Cardiovascular Risk in Humans as in Obese Mice

Autor: Ellen Thompson, John A. McClung, Nader G. Abraham, Giancarlo Acosta‐Baez, Yosef Glick, Shailendra P. Singh, Basel Edris, Menachem Greenberg, Joseph I. Shapiro
Rok vydání: 2019
Předmět:
Male
Cardiac function curve
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Mice
Obese
Adipose tissue
Adipokine
Medicine (miscellaneous)
030209 endocrinology & metabolism
Intra-Abdominal Fat
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Risk Factors
Internal medicine
Gene expression
medicine
Animals
Humans
Obesity
030212 general & internal medicine
Receptor
Aged
Obese Mice
Nutrition and Dietetics
business.industry
Myocardium
Original Articles
Middle Aged
medicine.disease
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Epicardial fat
Mice
Inbred C57BL
Heme oxygenase
Adipose Tissue
Cardiovascular Diseases
Cytoprotection
Heart failure
Original Article
Obesity Biology and Integrated Physiology
Female
Signal transduction
business
Pericardium
Heme Oxygenase-1
Signal Transduction
Zdroj: Obesity (Silver Spring, Md.)
ISSN: 1930-739X
1930-7381
Popis: Objective This study investigated whether levels of signaling pathways and inflammatory adipokines in epicardial fat regulate cardiovascular risks in humans and mice. Methods Epicardial fat was obtained from the hearts of patients with heart failure requiring coronary artery bypass surgery, and signaling pathways were compared with visceral fat. The genetic profile of epicardial and visceral fat from humans was also compared with genetic profiles of epicardial and visceral fat in obese mice. Left ventricular (LV) fractional shortening was measured in obese mice before and after treatment with inducers of mitochondrial signaling heme oxygenase 1 (HO-1)-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). An RNA array/heat map on 88 genes that regulate adipose tissue function was used to identify a target gene network. Results Human epicardial fat gene profiling showed decreased levels of mitochondrial signaling of HO-1-PGC1α and increased levels of the inflammatory adipokine CCN family member 3. Similar observations were seen in epicardial and visceral fat of obese mice. Improvement in LV function was linked to the increase in mitochondrial signaling in epicardial fat of obese mice. Conclusions There is a link between cardiac ectopic fat deposition and cardiac function in humans that is similar to that which is described in obese mice. An increase of mitochondrial signaling pathway gene expression in epicardial fat attenuates cardiometabolic dysfunction and LV fractional shortening in obese mice.
Databáze: OpenAIRE
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