Cited by 237Sirtuins and Resveratrol in MedicineRegulation of Appetite and ObesityGenetics, Aging, and Longevity in Model Organisms

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SIRT1 Promotes the Central Adaptive Response to Diet Restriction through Activation of the Dorsomedial and Lateral Nuclei of the Hypothalamus

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Satoh, Akiko, Brace, Cynthia S., Ben-Josef, Gal, West, Tim, Wozniak, David F., Holtzman, David M., Herzog, Erik D., Imai, Shin-ichiro·2010·The Journal of Neuroscience

DOI 10.1523/jneurosci.1385-10.2010PMC PMC2922851

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Abstract

Diet restriction retards aging and extends lifespan by triggering adaptive mechanisms that alter behavioral, physiological, and biochemical responses in mammals. Little is known about the molecular pathways evoking the corresponding central response. One factor that mediates the effects of diet restriction is the mammalian nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1. Here we demonstrate that diet restriction significantly increases SIRT1 protein levels and induces neural activation in the dorsomedial and lateral hypothalamic nuclei. Increasing SIRT1 in the brain of transgenic (BRASTO) mice enhances neural activity specifically in these hypothalamic nuclei, maintains a higher range of body temperature, and promotes physical activity in response to different diet-restricting paradigms. These responses are all abrogated in Sirt1-deficient mice. SIRT1 upregulates expression of the orexin type 2 receptor specifically in these hypothalamic nuclei in response to diet-restricting conditions, augmenting response to ghrelin, a gut hormone whose levels increase in these conditions. Our results suggest that in the hypothalamus, SIRT1 functions as a key mediator of the central response to low nutritional availability, providing insight into the role of the hypothalamus in the regulation of metabolism and aging in mammals.

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Authors: Satoh, A., Brace, C. S., Ben-Josef, G., West, T., Wozniak, D. F., Holtzman, D. M., Herzog, E. D., & Imai, S.-I.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Imai, Shin-ichiro
ORCID: Satoh, Akiko
West, Tim
Wozniak, David F.
Holtzman, David M.
Herzog, Erik D.
Imai, Shin-ichiro
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2010-07-28
Volume: 30
Issue: 30
Pages: 10220-10232
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.1385-10.2010
PMC: PMC2922851
OpenAlex: W2082921977
Cited by: 237
References: 66
Citations by year: 2026: 4 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 13 · 2020: 20 · 2019: 9 · 2018: 20 · 2017: 9 · 2016: 18 · 2015: 13 · 2014: 23 · 2013: 16 · 2012: 25
FWCI: 8.70
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Funders: Ellison Medical Foundation
Longer Life Foundation
Japan Society for the Promotion of Science
National Institute on Aging (R01AG024150, AG02150)
National Institute of Mental Health (R01MH063104)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: SIRT1, dietary restriction, hypothalamus, dorsomedial hypothalamus, lateral hypothalamic nucleus, ghrelin, NAD+-dependent deacetylase, aging, lifespan extension, body temperature, physical activity, metabolic regulation, neuronal activation
MeSH terms: Adaptation, Physiological, Animals, Body Temperature, Brain, Dorsomedial Hypothalamic Nucleus, Enzyme-Linked Immunosorbent Assay, Female, Food Deprivation, Hypothalamic Area, Lateral, Male, Mice, Inbred C57BL, Motor Activity, Neurons, RNA, Messenger, Up-Regulation, Receptors, Neuropeptide, Statistics, Nonparametric, Microdissection, Receptors, G-Protein-Coupled, Chromatin Immunoprecipitation, Mice, Ghrelin, Sirtuin 1, Orexin Receptors

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SIRT1 Promotes the Central Adaptive Response to Diet Restriction through Activation of the Dorsomedial and Lateral Nuclei of the Hypothalamus

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