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.
Keywords: ABW; ACC; AS160; ATP; Akt; Akt substrate 160; B2M; C/EBPβ; CCAAT/enhancer binding protein; CD36; CPT-I; Cardiac fatty acid metabolism; Cardiac glucose metabolism; FATP1; GLUT; GS; GSK; HPRT; HSL; IR; LBW; Left ventricular hypertrophy; Low birth weight; MNE; PAS; PC; PDH; PDK-4; PGC-1; PGK; PPAR; PPARγ coactivator 1; PPIA; RXRα; SD; TCA; YWAHZ; acetyl CoA carboxylase; adenosine triphosphate; average birth weight; beta-2-microglobulin; carnitine palmitoyltransferase-I; fatty acid translocase CD36; fatty acid transporter protein 1; glucose transporter; glycogen synthase; glycogen synthase kinase; hormone sensitive lipase; hypoxanthine phosphoribosyltransferase 1; insulin-receptor; low birth weight; mean normalised expression; peptidylprolyl isomerase A; periodic acid-Schiff; peroxisome proliferator activated receptor; phosphoglycerate kinase 1; protein kinase B; pyruvate carboxylase; pyruvate dehydrogenase; pyruvate dehydrogenase kinase-4; retinoid X receptor α; standard deviation; tricarboxylic acid; tyrosine 3-monooxygenase.
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