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F Bogazzi, Department of Endocrinology, University of Pisa, Pisa, 56124, Italy
F Raggi, Department of Endocrinology, University of Pisa, Pisa, Italy
F Ultimieri, Department of Endocrinology, University of Pisa, Pisa, Italy
D Russo, Department of Endocrinology, University of Pisa, Pisa, Italy
A D'Alessio, Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
A Manariti, Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
S Brogioni, Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
L Manetti, Department of Endocrinology, University of Pisa, Pisa, Italy
E Martino, Department of Endocrinology, University of Pisa, Pisa, Italy

Correspondence: Fausto Bogazzi, Email: fbogazzi{at}hotmail.com

Cardiac energy metabolism depends mainly on fatty acids(FA) oxidation; however, regulation of FA metabolism in acromegalic heart is unknown.

Aim of the study was to evaluate cardiac expression of key-proteins of FA metabolism in young and elder transgenic mice overexpressing bovine GH (Acro).

Expression of proteins regulating FA entry into the cells, their uptake by mitochondria and β-oxidation was evaluated by Western blot while FA content by FTIR-M. Regulatory mechanisms of key-steps of FA metabolism were also studied.

The expression of plasma-membrane FA carriers (FABP and FATP1) and acylCoA syntetase was higher in young and lower in elder Acro than in corresponding controls; likewise, expression of CPT-1, the key-enzyme of mitochondrial FA uptake, and that of MCAD and LCAD, two regulatory β-oxidation dehydrogenases, followed a similar pattern. FA content was lower in young and higher in elder Acro than in Wt, suggesting an increased utilization in young animals. GH regulated expression of key-proteins of FA metabolism through changes in PPAR expression, which varied accordingly. GH effect was confirmed by treatment of Acro mice with a receptor antagonist, which abolished changes in key-proteins of FA metabolism in young Acro. GH increased phosphorilation of AMPK and ACC, two regulatory kinases, leading to lower CPT-1 inhibition by malonylCoA, and intervened in regulating PPAR expression through the ERK1/2 pathway.

In conclusion, chronic GH excess increased FA metabolism in the young age, whereas its action was overwhelmed in elder ages likely by GH-independent mechanisms, leading to reduced expression of key-enzyme of FA metabolism.