Globular and full-length forms of adiponectin mediate specific changes in glucose and fatty acid uptake and metabolism in cardiomyocytes
Abstract
OBJECTIVE: Our aim was to investigate the regulation of glucose and fatty acid metabolism in cardiomyocytes by the globular (gAd) and full-length (fAd) forms of adiponectin. METHODS: We produced fAd (consisting of high, medium and low molecular weight oligomers) in a mammalian expression system and gAd in bacteria. These were used to treat primary neonatal rat cardiomyocytes (up to 48 h), and we employed 3H- or 14C-labeled substrates to monitor glucose uptake and subsequent metabolism via oxidation, glycogen synthesis or lactate production and fatty acid uptake and oxidation. Enzymatic assay for acetyl CoA carboxylase activity was employed, and protein phosphorylation and expression was determined by immunoblotting cell lysates. The role of adiponectin receptor (AdipoR) isoforms was determined via siRNA-mediated knockdown. RESULTS: There was an initial (1 h) increase in glucose uptake and oxidation in response to gAd or fAd. Fatty acid uptake was stimulated by gAd or fAd, and by 24 h a decrease in acetyl CoA carboxylase activity and elevated fatty acid oxidation were observed. After 48 h increased fatty acid oxidation correlated with decreased glucose oxidation and pyruvate dehydrogenase activity, while glycogen synthesis and lactate production increased. Both gAd and fAd elicited phosphorylation of AMP kinase, insulin receptor substrate-1, Akt and glycogen synthase kinase-3beta. Knockdown of AdipoR1 or AdipoR2 attenuated the effect of both gAd and fAd on fatty acid uptake and oxidation. Only AdipoR1 knockdown prevented the ability of gAd (1 h) to increase glucose uptake and oxidation; however, reducing either AdipoR1 or AdipoR2 expression attenuated the long-term (24 h) effects of gAd. CONCLUSIONS: These results clearly demonstrate that gAd and fAd mediate distinct and time-dependent effects on cardiomyocyte energy metabolism via AdipoR1 and AdipoR2.
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In neonatal rat cardiomyocytes, both full-length and globular adiponectin elicited an acute increase in glucose uptake and oxidation; after prolonged treatment, increased fatty acid uptake and oxidation predominated and correlated with decreased PDH activity and glucose oxidation; these effects were mediated via both AdipoR1 and AdipoR2 and occurred via signaling mechanisms involving AMPK, ACC,和A
“We have recently examined the effect of specific forms of adiponectin on metabolism in neonatal rat cardiomyocytes and found that both full-length and globular adiponectin elicited an acute increase in glucose uptake and oxidation (271). After prolonged treatment, increased fatty acid uptake and oxidation predominated and correlated with decreased PDH activity and glucose oxidation. Collectively,”
From Cardiac remodeling in obesity (2008) · cites this paper as [271]
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Self-citation
- Authors
- PALANIVEL, R., FANG, X., PARK, M., EGUCHI, M., PALLAN, S., DEGIROLAMO, S., LIU, Y., WANG, Y., XU, A., & SWEENEY, G.
- Affiliations
- York University (CA)
- University of Hong Kong (HK)
- Corresponding author
- SWEENEY, G
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-07-01
- Volume
- 75
- Issue
- 1
- Pages
- 148-157
- ISSN
- 0008-6363 (ISSN-L)
- OpenAlex
- W2034718314
- Cited by
- 117
- References
- 39
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 3 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 10
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adiponectin, globular adiponectin, cardiomyocytes, glucose uptake, fatty acid uptake, glucose oxidation, fatty acid oxidation, glycogen synthesis, lactic acid production, acetyl-CoA carboxylase, AMP kinase, IRS-1, Akt, glycogen synthase kinase-3β, AdipoR1, AdipoR2, cardiomyocyte energy metabolism
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Glucose, Molecular Weight, Oxidation-Reduction, Palmitates, Phosphorylation, Receptors, Cell Surface, RNA, Messenger, Time Factors, Blotting, Western, Rats, Sprague-Dawley, Protein Structure, Tertiary, CD36 Antigens, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Cardiac, RNA Interference, RNA, Small Interfering, Fatty Acid Transport Proteins, Rats, Adiponectin, Receptors, Adiponectin
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