Tags

Type your tag names separated by a space and hit enter

Exposure to rosiglitazone, a PPAR-γ agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus.
Am J Physiol Regul Integr Comp Physiol. 2014 Mar 15; 306(6):R429-37.AJ

Abstract

It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca(2+) sensitivity and maximum Ca(2+)-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and cardiomyocyte size. These findings suggest that activation of PPAR-γ using rosiglitazone does not promote the maturation of cardiomyocytes; rather, it may decrease cardiac metabolism and compromise cardiac health later in life.

Authors+Show Affiliations

Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; and.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24477540

Citation

Lie, Shervi, et al. "Exposure to Rosiglitazone, a PPAR-γ Agonist, in Late Gestation Reduces the Abundance of Factors Regulating Cardiac Metabolism and Cardiomyocyte Size in the Sheep Fetus." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 306, no. 6, 2014, pp. R429-37.
Lie S, Hui M, McMillen IC, et al. Exposure to rosiglitazone, a PPAR-γ agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus. Am J Physiol Regul Integr Comp Physiol. 2014;306(6):R429-37.
Lie, S., Hui, M., McMillen, I. C., Muhlhausler, B. S., Posterino, G. S., Dunn, S. L., Wang, K. C., Botting, K. J., & Morrison, J. L. (2014). Exposure to rosiglitazone, a PPAR-γ agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 306(6), R429-37. https://doi.org/10.1152/ajpregu.00431.2013
Lie S, et al. Exposure to Rosiglitazone, a PPAR-γ Agonist, in Late Gestation Reduces the Abundance of Factors Regulating Cardiac Metabolism and Cardiomyocyte Size in the Sheep Fetus. Am J Physiol Regul Integr Comp Physiol. 2014 Mar 15;306(6):R429-37. PubMed PMID: 24477540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exposure to rosiglitazone, a PPAR-γ agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus. AU - Lie,Shervi, AU - Hui,Melisa, AU - McMillen,I Caroline, AU - Muhlhausler,Beverly S, AU - Posterino,Giuseppe S, AU - Dunn,Stacey L, AU - Wang,Kimberley C, AU - Botting,Kimberley J, AU - Morrison,Janna L, Y1 - 2014/01/29/ PY - 2014/1/31/entrez PY - 2014/1/31/pubmed PY - 2014/5/20/medline KW - adiponectin KW - binucleated KW - contractility KW - fatty acid KW - fetus KW - glucose transporter KW - insulin KW - mononucleated KW - pregnancy KW - programming SP - R429 EP - 37 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am J Physiol Regul Integr Comp Physiol VL - 306 IS - 6 N2 - It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca(2+) sensitivity and maximum Ca(2+)-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and cardiomyocyte size. These findings suggest that activation of PPAR-γ using rosiglitazone does not promote the maturation of cardiomyocytes; rather, it may decrease cardiac metabolism and compromise cardiac health later in life. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/24477540/Exposure_to_rosiglitazone_a_PPAR_γ_agonist_in_late_gestation_reduces_the_abundance_of_factors_regulating_cardiac_metabolism_and_cardiomyocyte_size_in_the_sheep_fetus_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.00431.2013?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -