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Molecular and anatomical determinants of central leptin resistance
Abstract
The increasing incidence of obesity in developed nations is an ever-growing challenge to health care, promoting diabetes and other diseases. The hormone leptin, which is derived from adipose tissue, regulates feeding and energy expenditure. Most forms of obesity are associated with diminished responsiveness to the appetite-suppressing effects of leptin. Here we review the mechanisms by which leptin activates intracellular signals, the roles of these signals in leptin action in vivo, and mechanisms that may attenuate leptin signaling, limiting its action in obese individuals. We highlight data regarding the expression of SOCS3 (a potential mediator of leptin resistance) in the arcuate nucleus of the hypothalamus.
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“The LepR is expressed in multiple regions of the forebrain and hindbrain, including the hypothalamus, brainstem vasomotor centres and intermediolateral nucleus (IML) of the spinal cord119,135,138 (FIG. 5a).”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [135]
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“The anorexic effects of acute leptin injections are attenuated in individuals with obesity135.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [135]
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“However, obese subjects have higher cerebrospinal fluid (CSF) leptin levels compared to lean subjects102 suggesting that obesity also causes resistance to leptin signaling, likely related to a post-receptor defect103.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [103]
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Metadata
- Authors
- Münzberg, H., & Myers, M. G.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Myers, Martin G
- Venue
- Nature Neuroscience
- Published
- 2005-04-26
- Volume
- 8
- Issue
- 5
- Pages
- 566-570
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2042893069
- Semantic Scholar
- 71b5dabe299be6d5e8f778fa2686a524e8e2be92
- Cited by
- 550
- References
- 66
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 16 · 2019: 18 · 2018: 10 · 2017: 18 · 2016: 27 · 2015: 36 · 2014: 40 · 2013: 29 · 2012: 30
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin resistance, leptin signaling, obesity, SOCS3, arcuate nucleus, hypothalamus, appetite regulation, energy expenditure, intracellular signaling
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Adipose Tissue, Animals, Appetite Regulation, Energy Metabolism, Humans, Hypothalamus, Obesity, Receptors, Cell Surface, Repressor Proteins, Transcription Factors, Signal Transduction, Leptin, Suppressor of Cytokine Signaling Proteins, Receptors, Leptin
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