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The hypothalamic arcuate nucleus: A key site for mediating leptin’s effects on glucose homeostasis and locomotor activity
Open accessAbstract
Leptin is required for normal energy and glucose homeostasis. The hypothalamic arcuate nucleus (ARH) has been proposed as an important site of leptin action. To assess the physiological significance of leptin signaling in the ARH, we used mice homozygous for a FLPe-reactivatable, leptin receptor null allele (Lepr(neo/neo) mice). Similar to Lepr(db/db) mice, these mice are obese, hyperglycemic, hyperinsulinemic, infertile, and hypoactive. To selectively restore leptin signaling in the ARH, we generated an adeno-associated virus expressing FLPe-recombinase, which was delivered unilaterally into the hypothalamus using stereotaxic injections. We found that unilateral restoration of leptin signaling in the ARH of Lepr(neo/neo) mice leads to a modest decrease in body weight and food intake. In contrast, unilateral reactivation markedly improved hyperinsulinemia and normalized blood glucose levels and locomotor activity. These data demonstrate that leptin signaling in the ARH is sufficient for mediating leptin's effects on glucose homeostasis and locomotor activity.
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“unilateral, selective restoration of leptin signaling to the ARC was found to have only modest effects on food intake and body weight, while it markedly improved hyperinsulinemia and normalized blood glucose levels (40).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [40]
In the citing paper
“Genetic studies in mice suggest that the arcuate hypothalamic nucleus plays a major role in mediating effects of leptin on glucose balance and on voluntary locomotor activity (Coppari et al., 2005), however the specific arcuate neurons responsible remain unspecified.”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
In the citing paper
“Moreover, unilateral restoration of leptin receptor expression in the ARC of leptin receptor deficient Leprdb/db mice leads to long term reduction of body weight and food intake (Coppari et al., 2005)”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
In the citing paper
“Restoration of leptin-receptors in arcuate neurons greatly increases voluntary locomotor activity in Leprdb/db mice (Coppari et al., 2005), but the specific neurons mediating this action remain unknown.”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
In the citing paper
“unilateral, not bilateral, restoration of endogenous leptin receptors in arcuate neurons of leptin-receptor deficient mice (Coppari et al., 2005) results in a phenotype”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
In the citing paper
“and a normalization of serum glucose levels”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
In the citing paper
“and of locomotor activity (Coppari et al., 2005).”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
In the citing paper
“restoration of endogenous leptin receptors solely in the arcuate nucleus, accomplished by stereotaxic delivery of adeno viruses expressing FLPe-recombinase in otherwise leptin-receptor deficient mice, also results in a partial reduction in body weight and food intake”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Coppari et al., 2005
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Metadata
- Authors
- Coppari, R., Ichinose, M., Lee, C. E., Pullen, A. E., Kenny, C. D., McGovern, R. A., Tang, V., Liu, S. M., Ludwig, T., Chua, S. C., Lowell, B. B., & Elmquist, J. K.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Columbia University (US)
- Corresponding author
- Lowell, Bradford B.
- Elmquist, Joel K.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 1
- Issue
- 1
- Pages
- 63-72
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2017709986
- Cited by
- 457
- References
- 52
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 13 · 2022: 11 · 2021: 12 · 2020: 23 · 2019: 22 · 2018: 15 · 2017: 28 · 2016: 22 · 2015: 25 · 2014: 23 · 2013: 23 · 2012: 36
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (R01MH061583, MH61583)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK56116, DK53301, P01DK056116, R01DK057621, DK57621, DK 26687, P30DK026687)
- 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, arcuate nucleus, hypothalamus, glucose homeostasis, locomotor activity, leptin receptor, adeno-associated virus, hyperinsulinemia, obesity, dietary intake, body weight, hyperglycemia, infertility
- MeSH terms
- Alleles, Animals, Arcuate Nucleus of Hypothalamus, Body Composition, Body Weight, Cell Nucleus, DNA Nucleotidyltransferases, Fertility, Glucose, Homeostasis, Homozygote, Hypothalamus, Immunohistochemistry, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Genetic, Motor Activity, Neurons, Oxygen Consumption, Receptors, Cell Surface, Time Factors, Signal Transduction, Leptin, Green Fluorescent Proteins, Mice, Receptors, Leptin
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