Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders.

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.

authors

Zhang Y,Guan Y,Pan S,Yan L,Wang P,Chen Z,Shen Q,Zhao F,Zhang X,Li J,Li J,Cai D,Zhang G

doi

10.1073/pnas.2004392117

subject

Has Abstract

pub_date

2020-08-18 00:00:00

pages

20149-20158

issue

33

eissn

0027-8424

issn

1091-6490

pii

2004392117

journal_volume

117

pub_type

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