Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders.
Proc Natl Acad Sci U S A
; 117(33): 20149-20158, 2020 08 18.
Article
in En
| MEDLINE
| ID: mdl-32747560
ABSTRACT
The C2 domain containing protein extended synaptotagmin (E-Syt) plays important roles in both lipid homeostasis and the intracellular signaling; however, its role in physiology remains largely unknown. Here, we show that hypothalamic E-Syt3 plays a critical role in diet-induced obesity (DIO). E-Syt3 is characteristically expressed in the hypothalamic nuclei. Whole-body or proopiomelanocortin (POMC) neuron-specific ablation of E-Syt3 ameliorated DIO and related comorbidities, including glucose intolerance and dyslipidemia. Conversely, overexpression of E-Syt3 in the arcuate nucleus moderately promoted food intake and impaired energy expenditure, leading to increased weight gain. Mechanistically, E-Syt3 ablation led to increased processing of POMC to α-melanocyte-stimulating hormone (α-MSH), increased activities of protein kinase C and activator protein-1, and enhanced expression of prohormone convertases. These findings reveal a previously unappreciated role for hypothalamic E-Syt3 in DIO and related metabolic disorders.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation
/
Synaptotagmins
/
Obesity
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2020
Document type:
Article
Affiliation country:
China