Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance
Open accessAbstract
Hypothalamic neuropeptides play essential roles in regulating energy and body weight balance. Energy imbalance and obesity have been linked to hypothalamic signaling defects in regulating neuropeptide genes; however, it is unknown whether dysregulation of neuropeptide exocytosis could be critically involved. This study discovered that synaptotagmin-4, an atypical modulator of synaptic exocytosis, is expressed most abundantly in oxytocin neurons of the hypothalamus. Synaptotagmin-4 negatively regulates oxytocin exocytosis, and dietary obesity is associated with increased vesicle binding of synaptotagmin-4 and thus enhanced negative regulation of oxytocin release. Overexpressing synaptotagmin-4 in hypothalamic oxytocin neurons and centrally antagonizing oxytocin in mice are similarly obesogenic. Synaptotagmin-4 inhibition prevents against dietary obesity by normalizing oxytocin release and energy balance under chronic nutritional excess. In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases.
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Oxytocin induces weight loss in rodents, and this effect may be related to increased energy expenditure and lipolysis in addition to appetite suppression.
“Oxytocin induces weight loss in rodents, and this effect may be related to increased energy expenditure and lipolyis in addition to appetite suppression(6, 7, 8, 9, 10, 11).”
From Oxytocin reduces caloric intake in men (2015) · cites this paper as [9]
Intra-brain action of OXT can lead to reversal of obesity and related glucose and insulin disorders in mouse models.
“our recent research demonstrated that the intra-brain action of OXT can lead to reversal of obesity as well as related glucose and insulin disorders in mouse models [14], [15].”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [14]
Metabolic benefits of OXT are significantly attributed to the central action of this peptide.
“although the metabolic benefits of OXT is significantly attributed to the central action of this peptide [14]”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [14]
OXT can work in the brain to improve the neural regulation of metabolism and thereby counteract obesity and obesity-related metabolic abnormalities in mouse models.
“Our research further demonstrated that OXT can work in the brain to improve the neural regulation of metabolism and thereby counteract obesity and obesity-related metabolic abnormalities in mouse models [14], [15].”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [14]
OXT treatment decreases rather than increases food intake.
“OXT treatment decreases rather than increases food intake [14].”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [14]
OXT has a therapeutic advantage over antipsychotic drugs in that OXT treatment decreases rather than increases food intake.
“OXT has a therapeutic advantage over antipsychotic drugs in that OXT treatment decreases rather than increases food intake [14].”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [14]
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References 64 · Cited by 208
- Authors
- Zhang, G., Bai, H., Zhang, H., Dean, C., Wu, Q., Li, J., Guariglia, S., Meng, Q., & Cai, D.
- Affiliations
- Albert Einstein College of Medicine (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Cai, Dongsheng
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 69
- Issue
- 3
- Pages
- 523-535
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4353647
- OpenAlex
- W2015172493
- Cited by
- 208
- References
- 64
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 12 · 2023: 7 · 2022: 12 · 2021: 23 · 2020: 12 · 2019: 13 · 2018: 18 · 2017: 12 · 2016: 17 · 2015: 12 · 2014: 18 · 2013: 15 · 2012: 12
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG031774)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078750)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- synaptotagmin 4, oxytocin, hypothalamus, energy balance, body weight regulation, diet-induced obesity, oxytocin neurons, obesity prevention
- MeSH terms
- Animals, Body Weight, Energy Metabolism, Exocytosis, Hypothalamus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neuropeptides, Obesity, Oxytocin, Synaptotagmins, Mice
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