Replacing SNAP-25b with SNAP-25a expression results in metabolic disease

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a key molecule in the solubleN-ethylmaleimide–sensitive factor attachment protein (SNARE) complex mediating fast Ca2+-triggered release of hormones and neurotransmitters, and both splice variants, SNAP-25a and SNAP-25b, can participate in this p...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-08, Vol.112 (31), p.E4326-E4335
Main Authors: Valladolid-Acebes, Ismael, Daraio, Teresa, Brismar, Kerstin, Harkany, Tibor, Ögren, Sven Ove, Hökfelt, Tomas G. M., Bark, Christina
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Adipocytes - pathology
Adipose Tissue, White - metabolism
Adipose Tissue, White - pathology
Adiposity
Animals
Biological Sciences
Blood Glucose - metabolism
Body Weight
Dyslipidemias - pathology
Energy Intake
Energy Metabolism
Feeding Behavior
Female
Homeostasis
Hormones
Hyperglycemia
Hypertrophy
Hypothalamus - metabolism
Insulin - metabolism
Insulin Secretion
Leptin - blood
Lipids
Liver - metabolism
Liver - pathology
Male
Medicin och hälsovetenskap
Metabolic Diseases - blood
Metabolic Diseases - metabolism
Mice, Obese
Neurotransmitters
Phenotype
PNAS Plus
Proteins
Receptors, Leptin - metabolism
Rodents
Synaptosomal-Associated Protein 25 - deficiency
Synaptosomal-Associated Protein 25 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Synaptosomal-associated protein of 25 kDa (SNAP-25) is a key molecule in the solubleN-ethylmaleimide–sensitive factor attachment protein (SNARE) complex mediating fast Ca2+-triggered release of hormones and neurotransmitters, and both splice variants, SNAP-25a and SNAP-25b, can participate in this process. Here we explore the hypothesis that minor alterations in the machinery mediating regulated membrane fusion can increase the susceptibility for metabolic disease and precede obesity and type 2 diabetes. Thus, we used a mouse mutant engineered to express normal levels of SNAP-25 but only SNAP-25a. These SNAP-25b–deficient mice were exposed to either a control or a high-fat/high-sucrose diet. Monitoring of food intake, body weight, hypothalamic function, and lipid and glucose homeostases showed that SNAP-25b–deficient mice fed with control diet developed hyperglycemia, liver steatosis, and adipocyte hypertrophy, conditions dramatically exacerbated when combined with the high-fat/high-sucrose diet. Thus, modified SNARE function regulating stimulus-dependent exocytosis can increase the vulnerability to and even provoke metabolic disease. When combined with a high-fat/high-sucrose diet, this vulnerability resulted in diabesity. Our SNAP-25b–deficient mouse may represent a diabesity model.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1511951112