The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
A leptin–BDNF pathway regulating sympathetic innervation of adipose tissue
Abstract
Mutations in the leptin gene (ob) result in a metabolic disorder that includes severe obesity 1, and defects in thermogenesis 2 and lipolysis 3, both of which are adipose tissue functions regulated by the sympathetic nervous system. However, the basis of these sympathetic-associated abnormalities remains unclear. Furthermore, chronic leptin administration reverses these abnormalities in adipose tissue, but the underlying mechanism remains to be discovered. Here we report that ob/ob mice, as well as leptin-resistant diet-induced obese mice, show significant reductions of sympathetic innervation of subcutaneous white and brown adipose tissue. Chronic leptin treatment of ob/ob mice restores adipose tissue sympathetic innervation, which in turn is necessary to correct the associated functional defects. The effects of leptin on innervation are mediated via agouti-related peptide and pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus. Deletion of the gene encoding the leptin receptor in either population leads to reduced innervation in fat. These agouti-related peptide and pro-opiomelanocortin neurons act via brain-derived neurotropic factor-expressing neurons in the paraventricular nucleus of the hypothalamus (BDNF PVH). Deletion of BDNF PVH blunts the effects of leptin on innervation. These data show that leptin signalling regulates the plasticity of sympathetic architecture of adipose tissue via a top-down neural pathway that is crucial for energy homeostasis.
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
“Recent studies revealed that high expression of BDNF within the ventromedial hypothalamic nucleus (VMH) enhanced the SNS output of lipolytic signalling [22].”
In the citing paper
“Among other tissues, this decrease was particularly evident in adipose tissue, consistent with previous reports documenting decreased adipose-tissue innervation in obesity25–27.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [26]
Citations
Cites
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
Self-citationEffects 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
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
Self-citationPhysiological 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-citationLeptin receptor signaling in POMC neurons is required for normal body weight homeostasis
Balthasar, N., Coppari, R., McMinn, J., Liu, S. M., Lee, C. E., Tang, V., Kenny, C. D., McGovern, R. A., Chua, S. C., Elmquist, J. K., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.004 · Cited by 935
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737
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-citationSelective 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-citationSympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis
Zeng, W., Pirzgalska, R. M., Pereira, M. M. A., Kubasova, N., Barateiro, A., Seixas, E., Lu, Y.-H., Kozlova, A., Voss, H., Martins, G. G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.055 · Cited by 490
Self-citationCazorla, M., Prémont, J., Mann, A., Girard, N., Kellendonk, C., & Rognan, D. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43992 · Cited by 392
Cited by
Sorted by citations
Items 101–102 of 102
Cheng, B., Du, J., Tian, S., Zhang, Z., Chen, W., & Liu, Y. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02397-2 · Cited by 12
A deep-learning framework reveals whole-body perturbations at cell level
Kaltenecker, D., Horvath, I., Al-Maskari, R., Chen, Y., Kolabas, Z. I., Hoeher, L., Todorov, M., Minde, D.-P., Kapoor, S., Turhan, S. G., et al. (2026) · Nature · doi:10.1038/s41586-026-10535-2 · Cited by 5
Metadata
- Authors
- Wang, P., Loh, K. H., Wu, M., Morgan, D. A., Schneeberger, M., Yu, X., Chi, J., Kosse, C., Kim, D., Rahmouni, K., Cohen, P., & Friedman, J.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Iowa (US)
- Rockefeller University (US)
- Corresponding author
- Loh, Ken H.
- Friedman, Jeffrey
- ORCID
- Venue
- Nature
- Published
- 2020-07-22
- Volume
- 583
- Issue
- 7818
- Pages
- 839-844
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3044817976
- Cited by
- 332
- References
- 34
- Citations by year
- 2026: 53 · 2025: 44 · 2024: 72 · 2023: 52 · 2022: 54 · 2021: 47 · 2020: 10
- FWCI
- 20.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, brain-derived neurotrophic factor, sympathetic innervation, adipose tissue, agouti-related protein, proopiomelanocortin neurons, hypothalamic arcuate nucleus, paraventricular nucleus, leptin receptor, obesity, energy homeostasis, thermogenesis, lipolysis, leptin resistance
- MeSH terms
- Adipose Tissue, Animals, Arcuate Nucleus of Hypothalamus, Lipolysis, Male, Mice, Inbred C57BL, Neurons, Pro-Opiomelanocortin, Sympathetic Nervous System, Signal Transduction, Brain-Derived Neurotrophic Factor, Leptin, Thermogenesis, Subcutaneous Fat, Mice, Agouti-Related Protein
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
