The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation
Open accessAbstract
The contribution of different leptin-induced signaling pathways in control of energy homeostasis is only partly understood. Here we show that selective Pten ablation in leptin-sensitive neurons (Pten(DeltaObRb)) results in enhanced Pi3k activation in these cells and reduces adiposity by increasing energy expenditure. White adipose tissue (WAT) of Pten(DeltaObRb) mice shows characteristics of brown adipose tissue (BAT), reflected by increased mitochondrial content and Ucp1 expression resulting from enhanced leptin-stimulated sympathetic nerve activity (SNA) in WAT. In contrast, leptin-deficient ob/ob-Pten(DeltaObRb) mice exhibit unaltered body weight and WAT morphology compared to ob/ob mice, pointing to a pivotal role of endogenous leptin in control of WAT transdifferentiation. Leanness of Pten(DeltaObRb) mice is accompanied by enhanced sensitivity to insulin in skeletal muscle. These data provide direct genetic evidence that leptin-stimulated Pi3k signaling in the CNS regulates energy expenditure via activation of SNA to perigonadal WAT leading to BAT-like differentiation of WAT.
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
“Selective PTEN ablation in leptin-expressing neurons results in a phenotype characterized by reduced adiposity and increased energy expenditure due, at least in part, to increased fatty acid oxidation in WAT (144)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [144]
In the citing paper
“associated with increased sympathetic nerve activity to WAT and leading to a remodeling of WAT to take on characteristics of BAT, including increased mitochondrial content and UCP1 expression (144).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [144]
Citations
Cites
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
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Bates, S. H., Stearns, W. H., Dundon, T. A., Schubert, M., Tso, A. W. K., Wang, Y., Banks, A. S., Lavery, H. J., Haq, A. K., Maratos-Flier, E., et al. (2003) · Nature · doi:10.1038/nature01388 · Cited by 1,010
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979
Self-citationAgouti-related peptide–expressing neurons are mandatory for feeding
Gropp, E., Shanabrough, M., Borók, E., Xu, A. W., Janoschek, R., Buch, T., Plum, L., Balthasar, N., Hampel, B., Waisman, A., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1548 · Cited by 800
Self-citationFei, H., Okano, H. J., Li, C., Lee, G.-H., Zhao, C., Darnell, R., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.7001 · Cited by 766
Insulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production
Könner, A. C., Janoschek, R., Plum, L., Jordan, S. D., Rother, E., Ma, X., Xu, C., Enriori, P., Hampel, B., Barsh, G. S., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.004 · Cited by 695
Self-citationRole for neuronal insulin resistance in neurodegenerative diseases
Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., Schubert, D., Kondo, T., Alber, J., Galldiks, N., Küstermann, E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308724101 · Cited by 659
Self-citationWidespread recombinase expression using FLPeR (Flipper) mice
Farley, F. W., Soriano, P. M., Steffen, L. S., & Dymecki, S. M. (2000) · genesis · doi:10.1002/1526-968x(200011/12)28:3/4 · Cited by 602
Cited by
Sorted by citations
Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and Reproduction
Xu, Y., Nedungadi, T. P., Zhu, L., Sobhani, N., Irani, B. G., Davis, K. E., Zhang, X., Zou, F., Gent, L. M., Hahner, L. D., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.009 · Cited by 597
“For example, increased lipolysis in gonadal WAT is associated with elevated sympathetic inputs (Plum et al., 2007), while the expanded gonadal WAT is found to have decreased sympathetic inputs (Ramadori et al., 2010).”
BackgroundJordan, S. D., Krüger, M., Willmes, D. M., Redemann, N., Wunderlich, F. T., Brönneke, H. S., Merkwirth, C., Kashkar, H., Olkkonen, V. M., Böttger, T., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2211 · Cited by 531
“Dissected white- and brown-adipose-tissue samples were incubated in fixation solution containing 4p paraformaldehyde at 4 °C overnight, embedded in paraffin and sliced according to a previously described standard protoco”
MethodSelf-citationRecent advances in understanding leptin signaling and leptin resistance
Morris, D. L., & Rui, L. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00274.2009 · Cited by 484
Structure, production and signaling of leptin
Münzberg, H., & Morrison, C. D. (2014) · Metabolism · doi:10.1016/j.metabol.2014.09.010 · Cited by 486
Self-citationSignaling pathways in obesity: mechanisms and therapeutic interventions
Wen, X., Zhang, B., Wu, B., Xiao, H., Li, Z., Li, R., Xu, X., & Li, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01149-x · Cited by 490
“In contrast, PTEN knockout in hypothalamic leptin-sensitive neurons increases PI3K activity and leads to browning of WAT and weight loss.(132) A possible explanation is that systemic overexpression of PTEN exerts opposing effects in both the central and peripheral systems, but is more potent in the latter.”
Background
Metadata
- Authors
- Plum, L., Rother, E., Münzberg, H., Wunderlich, F. T., Morgan, D. A., Hampel, B., Shanabrough, M., Janoschek, R., Könner, A. C., Alber, J., Suzuki, A., Krone, W., Horvath, T. L., Rahmouni, K., & Brüning, J. C.
- Affiliations
- University of Cologne (DE)
- University of Michigan (US)
- University of Iowa (US)
- Yale University (US)
- Akita University (JP)
- Corresponding author
- Brüning, Jens C.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 6
- Issue
- 6
- Pages
- 431-445
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2160824260
- Cited by
- 138
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 4 · 2021: 13 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 8 · 2012: 11
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, PI3K signaling, PTEN, white adipose tissue, energy expenditure, sympathetic activity, leptin receptor neurons, ob/ob mice, insulin sensitivity, skeletal muscle, mitochondrial content, UCP1, energy homeostasis
- MeSH terms
- Animals, Adipose Tissue, Brown, Central Nervous System, Enzyme Activation, Glucose, Mice, Mutant Strains, Mice, Obese, Mice, Transgenic, Thinness, Signal Transduction, Mice, Knockout, Phosphatidylinositol 3-Kinases, Leptin, PTEN Phosphohydrolase, Mice, Adipose Tissue, White, Cell Transdifferentiation
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
