Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance

Bjørbæk, Christian; Elmquist, Joel K; Frantz, J.Daniel; Shoelson, Steven E; Flier, Jeffrey S

doi:10.1016/s1097-2765(00)80062-3

Cited by 1,014Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and Interactions

Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance

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Bjørbæk, Christian, Elmquist, Joel K, Frantz, J.Daniel, Shoelson, Steven E, Flier, Jeffrey S·1998·Molecular Cell

DOI 10.1016/s1097-2765(00)80062-3

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Abstract

Leptin affects food intake and body weight by actions on the hypothalamus. Although leptin resistance is common in obesity, mechanisms have not been identified. We examined the effect of leptin on expression of the suppressors-of-cytokine-signaling (SOCS) family of proteins. Peripheral leptin administration to ob/ob, but not db/db mice, rapidly induced SOCS-3 mRNA in hypothalamus, but had no effect on CIS, SOCS-1, or SOCS-2. A leptin-dependent increase of SOCS-3 mRNA was seen in areas of hypothalamus expressing high levels of the leptin receptor long form. In mammalian cell lines, SOCS-3, but not CIS or SOCS-2, blocked leptin-induced signal transduction. Expression of SOCS-3 mRNA in the arcuate and dorsomedial hypothalamic nuclei is increased in Ay/a mice, a model of leptin-resistant murine obesity. In conclusion, SOCS-3 is a leptin-inducible inhibitor of leptin signaling, and a potential mediator of leptin resistance in obesity.

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Cellular effects of leptin are amplified in cells lacking either SOCS3 or PT1b.
“Consistent with this, the cellular effects of leptin have been amplified in cells lacking either SOCS3 or PT1b, a phosphotyrosine phosphatase.”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [46]
Mice with haploinsufficiency for either SOCS3 or PT1b are resistant to obesity, remain lean on a high-fat diet, and retain leptin sensitivity.
“Importantly, mice with haploinsufficiency for either of these genes are resistant to obesity, remain lean on a high-fat diet, and retain leptin sensitivity (46,47).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [46]

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Authors: Bjørbæk, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E., & Flier, J. S.
Affiliations: Beth Israel Deaconess Medical Center (US)
Joslin Diabetes Center (US)
Corresponding author: Flier, Jeffrey S
ORCID: Elmquist, Joel K
Shoelson, Steven E
Flier, Jeffrey S
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 1998-03
Volume: 1
Issue: 4
Pages: 619-625
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(00)80062-3
OpenAlex: W2041872947
Cited by: 1,014
References: 47
Citations by year: 2026: 12 · 2025: 15 · 2024: 11 · 2023: 14 · 2022: 21 · 2021: 21 · 2020: 14 · 2019: 30 · 2018: 22 · 2017: 36 · 2016: 31 · 2015: 29 · 2014: 32 · 2013: 48 · 2012: 51
FWCI: 21.14
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5617 d)
Locations: Molecular Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r29mh056537-01a1)
National Institute of Mental Health (MH-56537)
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK45943, R01DK045943, DK-R37-28082, R37DK028082)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords: leptin resistance, SOCS3, suppressor of cytokine signaling, hypothalamus, leptin signaling, obesity, leptin receptor, ob/ob mice, db/db mice, arcuate nucleus, dorsomedial hypothalamus, signal transduction inhibition
MeSH terms: Suppressor of Cytokine Signaling 3 Protein, Animals, DNA-Binding Proteins, Hypothalamus, Male, Mice, Inbred C57BL, Mice, Obese, Neurons, Obesity, Proteins, Recombinant Proteins, Repressor Proteins, RNA, Messenger, Transcription Factors, Signal Transduction, Trans-Activators, In Situ Hybridization, Immediate-Early Proteins, Genes, Reporter, COS Cells, Leptin, Suppressor of Cytokine Signaling Proteins, Mice

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Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance

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