The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1
Abstract
Leptin is a 16 kDa product of the obesity gene secreted primarily by adipocytes. We recently identified cardiomyocytes as a target for the direct hypertrophic effects of leptin and suggested that leptin may be a biological link between obesity and cardiovascular pathologies. Activation of the renin-angiotensin and endothelin systems is associated with development of cardiovascular diseases and plasma renin levels are elevated in obese individuals. We therefore determined possible interaction between these factors in mediating hypertrophy in cultured neonatal rat ventricular myocytes. Treatment for 24 h with leptin (3.1 nM), angiotensin II (100 nM) or endothelin-1 (ET-1, 10 nM) significantly increased cell area by 37%, 36% and 35%, respectively and significantly increased gene expression of myosin light chain-2 and alpha-skeletal actin as well as leucine incorporation. The hypertrophic effects of all three agents were prevented by leptin and a leptin triple mutant receptor antagonist whereas the AT(1) receptor blocker (Sar1-lle(8))-Ang II or the ET(A) receptor blocker BQ123 was ineffective against leptin-induced hypertrophy. Both angiotensin II and ET-1 significantly increased leptin levels in the culture medium by fivefold. Moreover, both angiotensin II and ET-1 increased the gene expression of the short form (OBRa) by 180% and long form (OBRb) of leptin receptors by 200%, and this increase was abolished by both leptin receptor and leptin antibodies and leptin triple mutant. Although both angiotensin II and ET-1 increased phosphorylation of MAPK (p38, ERK1/2 and JNK) and NF-kappaB, the ability of leptin blockade to attenuate the hypertrophic responses was generally dissociated from these effects suggesting an alternate, yet to be identified cellular pathway mediating this role of leptin. Our studies therefore suggest a novel autocrine function for leptin in mediating the hypertrophic effects of both angiotensin II and ET-1 in cardiac myocytes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Importantly, there is also a growing appreciation for the potential importance of autocrine and paracrine effects mediated by adipokines derived from myocardium itself or the larger pericardial fat mass in obese subjects (153, 220, 281, 285, 293).”
From Cardiac remodeling in obesity (2008) · cites this paper as [293]
In the citing paper
“Several reports have suggested that leptin directly induced hypertrophy in both human and rodent cardiomyocytes (217, 292, 293, 379).”
From Cardiac remodeling in obesity (2008) · cites this paper as [293]
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., et al. (1995) · Nature Medicine · doi:10.1038/nm1195-1155 · Cited by 3,725
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327
The stomach is a source of leptin
Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J., Bortoluzzi, M.-N., Moizo, L., Lehy, T., Guerre-Millo, M., MARCHAND‐BRUSTEL, Y. L., et al. (1998) · Nature · doi:10.1038/29547 · Cited by 1,242
Leptin: a review of its peripheral actions and interactions
Margetic, S., Gazzola, C., Pegg, G. G., & Hill, R. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0802142 · Cited by 1,022
Wallace, A. M., McMahon, A. D., Packard, C. J., Kelly, A., Shepherd, J., Gaw, A., & Sattar, N. A. (2001) · Circulation · doi:10.1161/hc5001.101061 · Cited by 821
Barouch, L. A., Berkowitz, D. E., Harrison, R. W., O’Donnell, C. P., & Hare, J. M. (2003) · Circulation · doi:10.1161/01.cir.0000083716.82622.fd · Cited by 341
The Obesity-Associated Peptide Leptin Induces Hypertrophy in Neonatal Rat Ventricular Myocytes
Rajapurohitam, V., Gan, X. T., Kirshenbaum, L. A., & Karmazyn, M. (2003) · Circulation Research · doi:10.1161/01.res.0000089255.37804.72 · Cited by 248
Self-citationLappas, M., Permezel, M., & Rice, G. E. (2005) · Endocrinology · doi:10.1210/en.2005-0406 · Cited by 241
Cited by
Sorted by citations
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736
Yang, R., & Barouch, L. A. (2007) · Circulation Research · doi:10.1161/circresaha.107.156596 · Cited by 334
Packer, M. (2018) · Circulation · doi:10.1161/circulationaha.117.032474 · Cited by 263
Cardiovascular effects of leptin
Sweeney, G. (2009) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2009.224 · Cited by 186
Luo, X., Lin, H., Pan, Z., Xiao, J., Zhang, Y., Lu, Y., Yang, B., & Wang, Z. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801035200 · Cited by 177
Retracted
Metadata
- Authors
- Rajapurohitam, V., Javadov, S., Purdham, D. M., Kirshenbaum, L. A., & Karmazyn, M.
- Affiliations
- Western University (CA)
- St. Boniface Hospital (CA)
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 41
- Issue
- 2
- Pages
- 265-274
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W2008347790
- Cited by
- 102
- References
- 43
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, cardiomyocyte hypertrophy, angiotensin II, endothelin-1, autocrine signaling, leptin receptor, obesity, renin-angiotensin system, endothelin system, MAPK signaling, NF-κB, myosin light chain 2, alpha-skeletal actin, ventricular myocytes
- MeSH terms
- Angiotensin II, Animals, Animals, Newborn, Cells, Cultured, Gene Expression Regulation, Cardiomegaly, Heart Ventricles, Obesity, Vasoconstrictor Agents, Rats, Sprague-Dawley, Adipocytes, Endothelin-1, Autocrine Communication, Leptin, MAP Kinase Signaling System, Myocytes, Cardiac, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
