The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Site and mechanism of leptin action in a rodent form of congenital lipodystrophy
Open accessAbstract
Lipodystrophy is characterized by the complete or partial absence of adipose tissue, insulin resistance, hepatic steatosis, and leptin deficiency. Here, we show that low-dose central leptin corrects the insulin resistance and fatty liver of lipodystrophic aP2-nSREBP-1c mice, while the same dose given peripherally does not. Central leptin also repressed stearoyl-CoA desaturase-1 (SCD-1) RNA and enzymatic activity, which were increased in livers of lipodystrophic mice. aP2-nSREBP-1c mice homozygous for an SCD-1 deletion had markedly reduced hepatic steatosis, increased saturated fatty acids, decreased acetyl-CoA carboxylase activity, and decreased malonyl-CoA levels in the liver. Despite the reduction in hepatic steatosis, these mice remained diabetic. A leptin dose-response curve showed that subcutaneous leptin improved hyperglycemia and hyperinsulinemia in aP2-nSREBP-1c mice at doses that did not substantially alter hepatic steatosis or hepatic SCD enzymatic activity. Leptin treatment at this dose improved insulin-stimulated insulin receptor and insulin receptor substrate 2 (IRS-2) phosphorylation, IRS-2–associated PI3K activity, and Akt activity in liver. Together, these data suggest that CNS-mediated repression of SCD-1 contributes to leptin's antisteatotic actions. Intracerebroventricular leptin improves glucose homeostasis by improving insulin signal transduction in liver, but in this case the effect appears to be independent of SCD-1.
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
“low-dose i.c.v. administration of leptin corrects the insulin resistance and diabetes phenotype of both leptin deficient ob/ob and lipodystrophic mice (2).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [2]
In the citing paper
“In rodent models, leptin increased expression of AMP-activated protein kinase (28) and peroxisome proliferator-activated receptor (PPAR) ␣ (29), activating enzymes of fatty acid oxidation, including carnitine palmitoyl transferase-1 and acyl-CoA oxidase, and inhibiting enzymes of lipogenesis, including acyl-CoA carboxylase and stearoyl-CoA desaturase-1 (28,30).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [30]
Citations
Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
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
Self-citationThe metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Nonalcoholic Fatty Liver Disease
Angulo, P. (2002) · New England Journal of Medicine · doi:10.1056/nejmra011775 · Cited by 5,228
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Self-citationCellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., & Schaffer, J. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630588100 · Cited by 2,075
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Nonalcoholic fatty liver disease
Adams, L. A. (2005) · Canadian Medical Association Journal · doi:10.1503/cmaj.045232 · Cited by 1,652
Leptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247
Brüning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Hörsch, D., Accili, D., Goodyear, L. J., & Kahn, C. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80155-0 · Cited by 1,183
Self-citationLoss of stearoyl–CoA desaturase-1 function protects mice against adiposity
Ntambi, J. M., Miyazaki, M., Stoehr, J. P., Hong, L., Kendziorski, C. M., Yandell, B. S., Song, Y., Cohen, P., Friedman, J. M., & Attie, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132384699 · Cited by 1,096
Self-citationLeptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., & Goldstein, J. L. (1999) · Nature · doi:10.1038/43448 · Cited by 1,038
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8878 · Cited by 1,033
Self-citationShimomura, I., Matsuda, M., Hammer, R. E., Bashmakov, Y. K., Brown, M. S., & Goldstein, J. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00010-9 · Cited by 860
Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss
Cohen, P., Miyazaki, M., Socci, N. D., Hagge-Greenberg, A., Liedtke, W., Soukas, A. A., Sharma, R., Hudgins, L. C., Ntambi, J. M., & Friedman, J. M. (2002) · Science · doi:10.1126/science.1071527 · Cited by 826
Self-citationLeptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
Petersen, K. F., Oral, E. A., Dufour, S., Befroy, D., Ariyan, C., Yu, C., Cline, G. W., DePaoli, A. M., Taylor, S. I., Gorden, P., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215001 · Cited by 800
Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., & Brown, M. S. (1998) · Genes & Development · doi:10.1101/gad.12.20.3182 · Cited by 790
Life without white fat: a transgenic mousePreprint
Moitra, J., Mason, M. M., Olive, M., Krylov, D. Y., Gavrilova, O., Marcus‐Samuels, B., Feigenbaum, L., Lee, E., Aoyama, T., Eckhaus, M., et al. (1998) · Genes & Development · doi:10.1101/gad.12.20.3168 · Cited by 776
Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol
Ntambi, J. M. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33401-5 · Cited by 762
Self-citationA possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.
McGarry, J. D., Mannaerts, G. P., & Foster, D. W. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108764 · Cited by 736
Friedman, J. M. (2000) · Nature · doi:10.1038/35007504 · Cited by 708
Self-citationAcute stimulation of glucose metabolism in mice by leptin treatment
Kamohara, S., Burcelin, R., Halaas, J. L., Friedman, J. M., & Charron, M. J. (1997) · Nature · doi:10.1038/38717 · Cited by 708
Self-citationSurgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
Gavrilova, O., Marcus-Samuels, B., Graham, D., Kim, J. K., Shulman, G. I., Castle, A. L., Vinson, C., Eckhaus, M., & Reitman, M. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7901 · Cited by 676
Selective deletion of leptin receptor in neurons leads to obesity
Cohen, P., Zhao, C., Cai, X., Montez, J. M., Rohani, S., Feinstein, P. G., Mombaerts, P., & Friedman, J. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13914 · Cited by 664
Self-citationMatsusue, K., Haluzik, M., Lambert, G., Yim, S.-H., Gavrilova, O., Ward, J. M., Brewer, B., Reitman, M. L., & Gonzalez, F. J. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317223 · Cited by 585
Kudo, N., Barr, A., Barr, R. L., Desai, S. S., & Lopaschuk, G. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17513 · Cited by 565
Selective deletion of leptin receptor in neurons leads to obesity
Cohen, P., Zhao, C., Cai, X., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113914 · Cited by 554
Self-citationLeptin-specific patterns of gene expression in white adipose tissuePreprint
Soukas, A. A., Cohen, P., Socci, N. D., & Friedman, J. M. (2000) · Genes & Development · doi:10.1101/gad.14.8.963 · Cited by 513
Self-citationZarjevski, N., Cusin, I., Vettor, R., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404618 · Cited by 476
Kieffer, T. J., Heller, R. S., Leech, C. A., Holz, G. G., & Habener, J. F. (1997) · Diabetes · doi:10.2337/diab.46.6.1087 · Cited by 395
Differentiation-induced Gene Expression in 3T3-L1 Preadipocytes
Kaestner, K. H., Ntambi, J. M., Kelly, T. J., & Lane, M. D. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63763-9 · Cited by 371
Self-citationNtambi, J. M., Buhrow, S. A., Kaestner, K. H., Christy, R. J., Sibley, E., Kelly, T. J., & Lane, M. D. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77834-x · Cited by 354
Self-citationMechanisms and regulation of biosynthesis of saturated fatty acids.
Volpe, J. J., & Vagelos, P. R. (1976) · Physiological Reviews · doi:10.1152/physrev.1976.56.2.339 · Cited by 341
Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype
Segal‐Lieberman, G., Bradley, R. L., Kokkotou, E. G., Carlson, M., Trombly, D. J., Wang, X., Bates, S. H., Myers, M. G., Flier, J. S., & Maratos–Flier, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1633636100 · Cited by 239
Ebihara, K., Ogawa, Y., Masuzaki, H., Shintani, M., Miyanaga, F., Aizawa‐Abe, M., Hayashi, T., Hosoda, K., Inoue, G., Yoshimasa, Y., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1440 · Cited by 238
Increased insulin sensitivity in mice lacking p85β subunit of phosphoinositide 3-kinase
Ueki, K., Yballe, C. M., Brachmann, S. M., Vicent, D., Watt, J. M., Kahn, C. R., & Cantley, L. C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012581799 · Cited by 229
Self-citationWitters, L. A., & Kemp, B. E. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50663-9 · Cited by 228
Ogawa, Y., Masuzaki, H., Hosoda, K., Aizawa‐Abe, M., Suga, J., Suda, M., Ebihara, K., Iwai, H., Matsuoka, N., Satoh, N., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1822 · Cited by 203
Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat.
Chinookoswong, N., Wang, J. L., & Shi, Z. Q. (1999) · Diabetes · doi:10.2337/diabetes.48.7.1487 · Cited by 197
McGarry, J., Stark, M. J., & Foster, D. W. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34394-6 · Cited by 188
PPARα is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue
Lee, Y., Yu, X., Gonzales, F., Mangelsdorf, D. J., Wang, M.-Y., Richardson, C., Witters, L. A., & Unger, R. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182420899 · Cited by 181
Atkinson, L. L., Fischer, M. A., & Lopaschuk, G. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203813200 · Cited by 174
Colombo, C., Cutson, J. J., Yamauchi, T., Vinson, C., Kadowaki, T., Gavrilova, O., & Reitman, M. L. (2002) · Diabetes · doi:10.2337/diabetes.51.9.2727 · Cited by 147
Lipoatrophic diabetes in Irs1−/−/Irs3−/− double knockout micePreprint
Laustsen, P. G., Michael, M. D., Crute, B. E., Cohen, S. E., Ueki, K., Kulkarni, R. N., Keller, S. R., Lienhard, G. E., & Kahn, C. R. (2002) · Genes & Development · doi:10.1101/gad.1034802 · Cited by 137
Self-citationLunzer, M., Manning, J. A., & Ockner, R. K. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63376-4 · Cited by 110
Miyazaki, M., Kim, H.-J., Man, W. C., & Ntambi, J. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106442200 · Cited by 109
Self-citationBurcelin, R., Kamohara, S., Li, J., Tannenbaum, G. S., Charron, M. J., & Friedman, J. M. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1264 · Cited by 92
Self-citationKieffer, T. J., Heller, R. S., Leech, C. A., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.6.1087 · Cited by 65
CNS melanocortin and leptin effects on stearoyl-CoA desaturase-1 and resistin expression
Lin, J., Choi, Y., Hartzell, D. L., Li, C., Della‐Fera, M. A., & Baile, C. A. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.10.004 · Cited by 42
Mechanism of glucoregulatory responses to stress and their deficiency in diabetes.
Miles, P. D. G., Yamatani, K., Lickley, H. L. A., & Vranić, M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.4.1296 · Cited by 38
Flagged first, then by citations
Cited by
Sorted by citations
What we talk about when we talk about fat
Rosen, E. D., & Spiegelman, B. M. (2014) · Cell · doi:10.1016/j.cell.2013.12.012 · Cited by 2,373
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
Mechanisms of obesity-associated insulin resistance: many choices on the menuPreprint
Qatanani, M., & Lazar, M. A. (2007) · Genes & Development · doi:10.1101/gad.1550907 · Cited by 798
Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 710
Leptin and the endocrine control of energy balance
Friedman, J. M. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0095-y · Cited by 661
Self-citation
Metadata
- Authors
- Asilmaz, E., Cohen, P., Miyazaki, M., Dobrzyn, P., Ueki, K., Fayzikhodjaeva, G., Soukas, A. A., Kahn, C. R., Ntambi, J. M., Socci, N. D., & Friedman, J. M.
- Affiliations
- Rockefeller University (US)
- University of Wisconsin System (US)
- Joslin Diabetes Center (US)
- Albert Einstein College of Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Friedman, Jeffrey M.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2004-02-01
- Volume
- 113
- Issue
- 3
- Pages
- 414-424
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2104945088
- Cited by
- 210
- References
- 51
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 9 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 9 · 2016: 13 · 2015: 8 · 2014: 13 · 2013: 12 · 2012: 5
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM07739, MSTPGM07739)
- National Institute of General Medical Sciences (GM 07739, T32GM007739)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-41096, R01DK062388, R01-DK-62388, R01DK041096)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- leptin, congenital lipodystrophy, insulin resistance, hepatic steatosis, stearoyl-CoA desaturase 1, glucose homeostasis, insulin receptor substrate 2, PI3K/Akt signaling, acetyl-CoA carboxylase, malonyl-CoA
- MeSH terms
- Animals, Disease Models, Animal, Female, Lipodystrophy, Liver, Male, Mice, Inbred C57BL, Phylogeny, Stearoyl-CoA Desaturase, Muscle, Skeletal, Leptin, Gene Expression Profiling, Mice
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
