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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0336v1 199/3/389    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sweeney, G. Articles by Vu, V. Search for Related Content PubMed PubMed Citation Articles by Sweeney, G. Articles by Vu, V.

G Sweeney, biology, York University, Toronto, Ontario, M3J1P3, Canada
R Palanivel, Toronto, Canada
X Fang, Toronto, Canada
M Park, Toronto, Canada
V Vu, toronto, Canada

Correspondence: Gary Sweeney, Email: gsweeney{at}yorku.ca

Abstract

The causal relationship between obesity and cardiovascular disease is extensively acknowledged, however the exact mechanisms linking obesity and heart failure remain unclear. Here we investigated the influence of adipokines derived from primary adipocytes on glucose and fatty acid uptake and metabolism in isolated primary cardiomyocytes. Either coculture of these cell types or incubation with adipocyte-conditioned medium significantly increased glucose uptake in cardiomyocytes. When streptozotocin-induced diabetic rats were used as source of adipocytes there was a lower ability to elicit glucose uptake in cardiomyocytes which corresponded with lower Akt and AMPK phosphorylation. The profile of glucose metabolism also differed with oxidation being favoured upon coculture with wild-type adipocytes whereas lactate production was strongly induced by adipocytes from diabetic rats. Examination of fatty acid uptake revealed that stimulation only occurred in response to adipokines secreted by wild-type rat adipocytes. Importantly, oxidation of fatty acids by cardiomyocytes was decreased by adipokines derived from diabetic rat adipocytes. Analysis of adipokine profiles in diabetic rat adipocyte-conditioned medium demonstrated most significant decreases in adiponectin and leptin with increased IL-6 expression. Taken together, these data suggest that the profile of adipokines secreted by adipocytes from diabetic rats have a deliterious influence on cardiomyocyte metabolism which may be of relevance in the pathophysiology of heart failure.