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Alteration of cardiac glucose metabolism in association to low birth weight: experimental evidence in lambs with left ventricular hypertrophy.
Metabolism. 2013 Nov; 62(11):1662-72.M

Abstract

OBJECTIVE

Intrauterine growth restriction that results in low birth weight (LBW) has been linked to the onset of pathological cardiac hypertrophy. An altered transition from a fetal to an adult energy metabolism phenotype, with increased reliance on glucose rather than fatty acids for energy production, could help explain this connection. We have therefore investigated cardiac metabolism in relation to left ventricular hypertrophy in LBW lambs, at 21days after birth.

MATERIALS/METHODS

The expression of regulatory molecules involved in cardiac glucose and fatty acid metabolism was measured using real-time PCR and Western blotting. A section of the left ventricle was fixed for Periodic Acid Schiff staining to determine tissue glycogen content.

RESULTS

There was increased abundance of insulin signalling pathway proteins (phospho-insulin receptor, insulin receptor and phospho-Akt) and the glucose transporter (GLUT)-1, but no change in GLUT-4 or glycogen content in the heart of LBW compared to ABW lambs. There was, however, increased abundance of cardiac pyruvate dehydrogenase kinase 4 (PDK-4) in LBW compared to ABW lambs. There were no significant changes in the mRNA expression of components of the peroxisome proliferator activated receptor regulatory complex or proteins involved in fatty acid metabolism.

CONCLUSION

We concluded that LBW induced left ventricular hypertrophy was associated with increased GLUT-1 and PDK-4, suggesting increased glucose uptake, but decreased efficacy for the conversion of glucose to ATP. A reduced capacity for energy conversion could have significant implications for vulnerability to cardiovascular disease in adults who are born LBW.

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, SA, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23928106

Citation

Wang, Kimberley C W., et al. "Alteration of Cardiac Glucose Metabolism in Association to Low Birth Weight: Experimental Evidence in Lambs With Left Ventricular Hypertrophy." Metabolism: Clinical and Experimental, vol. 62, no. 11, 2013, pp. 1662-72.
Wang KC, Lim CH, McMillen IC, et al. Alteration of cardiac glucose metabolism in association to low birth weight: experimental evidence in lambs with left ventricular hypertrophy. Metabolism. 2013;62(11):1662-72.
Wang, K. C., Lim, C. H., McMillen, I. C., Duffield, J. A., Brooks, D. A., & Morrison, J. L. (2013). Alteration of cardiac glucose metabolism in association to low birth weight: experimental evidence in lambs with left ventricular hypertrophy. Metabolism: Clinical and Experimental, 62(11), 1662-72. https://doi.org/10.1016/j.metabol.2013.06.013
Wang KC, et al. Alteration of Cardiac Glucose Metabolism in Association to Low Birth Weight: Experimental Evidence in Lambs With Left Ventricular Hypertrophy. Metabolism. 2013;62(11):1662-72. PubMed PMID: 23928106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alteration of cardiac glucose metabolism in association to low birth weight: experimental evidence in lambs with left ventricular hypertrophy. AU - Wang,Kimberley C W, AU - Lim,Chin H, AU - McMillen,I Caroline, AU - Duffield,Jaime A, AU - Brooks,Doug A, AU - Morrison,Janna L, Y1 - 2013/08/05/ PY - 2012/12/13/received PY - 2013/06/24/revised PY - 2013/06/29/accepted PY - 2013/8/10/entrez PY - 2013/8/10/pubmed PY - 2014/1/7/medline KW - ABW KW - ACC KW - AS160 KW - ATP KW - Akt KW - Akt substrate 160 KW - B2M KW - C/EBPβ KW - CCAAT/enhancer binding protein KW - CD36 KW - CPT-I KW - Cardiac fatty acid metabolism KW - Cardiac glucose metabolism KW - FATP1 KW - GLUT KW - GS KW - GSK KW - HPRT KW - HSL KW - IR KW - LBW KW - Left ventricular hypertrophy KW - Low birth weight KW - MNE KW - PAS KW - PC KW - PDH KW - PDK-4 KW - PGC-1 KW - PGK KW - PPAR KW - PPARγ coactivator 1 KW - PPIA KW - RXRα KW - SD KW - TCA KW - YWAHZ KW - acetyl CoA carboxylase KW - adenosine triphosphate KW - average birth weight KW - beta-2-microglobulin KW - carnitine palmitoyltransferase-I KW - fatty acid translocase CD36 KW - fatty acid transporter protein 1 KW - glucose transporter KW - glycogen synthase KW - glycogen synthase kinase KW - hormone sensitive lipase KW - hypoxanthine phosphoribosyltransferase 1 KW - insulin-receptor KW - low birth weight KW - mean normalised expression KW - peptidylprolyl isomerase A KW - periodic acid-Schiff KW - peroxisome proliferator activated receptor KW - phosphoglycerate kinase 1 KW - protein kinase B KW - pyruvate carboxylase KW - pyruvate dehydrogenase KW - pyruvate dehydrogenase kinase-4 KW - retinoid X receptor α KW - standard deviation KW - tricarboxylic acid KW - tyrosine 3-monooxygenase SP - 1662 EP - 72 JF - Metabolism: clinical and experimental JO - Metabolism VL - 62 IS - 11 N2 - OBJECTIVE: Intrauterine growth restriction that results in low birth weight (LBW) has been linked to the onset of pathological cardiac hypertrophy. An altered transition from a fetal to an adult energy metabolism phenotype, with increased reliance on glucose rather than fatty acids for energy production, could help explain this connection. We have therefore investigated cardiac metabolism in relation to left ventricular hypertrophy in LBW lambs, at 21days after birth. MATERIALS/METHODS: The expression of regulatory molecules involved in cardiac glucose and fatty acid metabolism was measured using real-time PCR and Western blotting. A section of the left ventricle was fixed for Periodic Acid Schiff staining to determine tissue glycogen content. RESULTS: There was increased abundance of insulin signalling pathway proteins (phospho-insulin receptor, insulin receptor and phospho-Akt) and the glucose transporter (GLUT)-1, but no change in GLUT-4 or glycogen content in the heart of LBW compared to ABW lambs. There was, however, increased abundance of cardiac pyruvate dehydrogenase kinase 4 (PDK-4) in LBW compared to ABW lambs. There were no significant changes in the mRNA expression of components of the peroxisome proliferator activated receptor regulatory complex or proteins involved in fatty acid metabolism. CONCLUSION: We concluded that LBW induced left ventricular hypertrophy was associated with increased GLUT-1 and PDK-4, suggesting increased glucose uptake, but decreased efficacy for the conversion of glucose to ATP. A reduced capacity for energy conversion could have significant implications for vulnerability to cardiovascular disease in adults who are born LBW. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/23928106/Alteration_of_cardiac_glucose_metabolism_in_association_to_low_birth_weight:_experimental_evidence_in_lambs_with_left_ventricular_hypertrophy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(13)00194-7 DB - PRIME DP - Unbound Medicine ER -