Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice
Open accessAbstract
Diet affects health through ingested calories and macronutrients, and macronutrient balance affects health span. The mechanisms regulating macronutrient-based diet choices are poorly understood. Previous studies had shown that NAD-dependent deacetylase sirtuin-1 (SIRT1) in part influences the health-promoting effects of caloric restriction by boosting fat use in peripheral tissues. Here, we show that neuronal SIRT1 shifts diet choice from sucrose to fat in mice, matching the peripheral metabolic shift. SIRT1-mediated suppression of simple sugar preference requires oxytocin signalling, and SIRT1 in oxytocin neurons drives this effect. The hepatokine FGF21 acts as an endocrine signal to oxytocin neurons, promoting neuronal activation and Oxt transcription and suppressing the simple sugar preference. SIRT1 promotes FGF21 signalling in oxytocin neurons and stimulates Oxt transcription through NRF2. Thus, neuronal SIRT1 contributes to the homeostatic regulation of macronutrient-based diet selection in mice.
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The core effect of FGF21 to suppress sweet and alcohol intake has been replicated by additional studies.
“this core effect of FGF21 to suppress sweet and alcohol intake has since been replicated by additional studies”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [181]
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- Authors
- Matsui, S., Sasaki, T., Kohno, D., Yaku, K., Inutsuka, A., Yokota-Hashimoto, H., Kikuchi, O., Suga, T., Kobayashi, M., Yamanaka, A., Harada, A., Nakagawa, T., Onaka, T., & Kitamura, T.
- Affiliations
- Gunma University (JP)
- University of Toyama (JP)
- Jichi Medical University (JP)
- Research Institute of Environmental Medicine, Nagoya University (JP)
- The University of Osaka (JP)
- Corresponding author
- Sasaki, Tsutomu
- Kitamura, Tadahiro
- ORCID
- Venue
- Nature Communications
- Published
- 2018-11-02
- Volume
- 9
- Issue
- 1
- Pages
- 4604-4604
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6214990
- OpenAlex
- W2899329365
- Cited by
- 72
- References
- 69
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 6 · 2023: 5 · 2022: 11 · 2021: 16 · 2020: 10 · 2019: 9
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- University of Michigan
- Japan Society for the Promotion of Science (16K08527, 17K08653, 17H01971, 17H06061, 15K19504, 17K16139, 18H02594, 17H06422, 16H06276)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- SIRT1, FGF21, oxytocin neurons, sucrose preference, fat preference, Nrf2, caloric restriction, NAD+-dependent deacetylase
- MeSH terms
- Klotho Proteins, Animals, Base Sequence, Choice Behavior, Diet, Fasting, Female, Fibroblast Growth Factors, Glucuronidase, Male, Mice, Inbred C57BL, Models, Biological, Neurons, Oxytocin, Paraventricular Hypothalamic Nucleus, Sucrose, Signal Transduction, Mice, Knockout, Proto-Oncogene Proteins c-akt, NF-E2-Related Factor 2, Sirtuin 1
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