Central nesfatin-1 activates lipid mobilization in adipose tissue and fatty acid oxidation in muscle via the sympathetic nervous system.
hypothalamic nucleus
lipid metabolism
nesfatin-1
sympathetic nervous system
type 2 diabetes mellitus
Journal
BioFactors (Oxford, England)
ISSN: 1872-8081
Titre abrégé: Biofactors
Pays: Netherlands
ID NLM: 8807441
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
01
11
2019
accepted:
09
12
2019
pubmed:
4
1
2020
medline:
23
4
2021
entrez:
4
1
2020
Statut:
ppublish
Résumé
Little is known about the influence of central nesfatin-1 on lipid metabolism under diabetic conditions. The main objective of this study was to characterize the mechanisms by which central nesfatin-1 regulates lipid metabolism in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) and whether the sympathetic nervous system is involved. Male Kunming mice were fed high-fat diets (HFDs) and were treated twice with low-dose STZ (100 mg/kg, intraperitoneal [IP]) to generate the T2DM model. Pharmacological adrenergic blockage (phentolamine 10 mg/kg, propranolol 0.017 mmol) and surgical denervation of sympathetic nervous system of the hindlimb and inguinal fat were used to block nerve conduction to determine whether the effect of central nesfatin-1 required the hypothalamic-sympathetic nervous system axis. Plasma free fatty acid (FFA) and insulin levels were measured. AMP-activated protein kinase (AMPK) levels in skeletal muscle and hormone-sensitive lipase and adipose triglycerides lipase (HSL/ATGL) levels in white adipose tissue (WAT) were measured using western blot. mRNA expression of AMPK was measured. We found that there were significantly fewer NUCB2/nesfatin-1 immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in T2DM mice. Central nesfatin-1 administration decreased levels of plasma FFA significantly and activated AMPK to enhance fatty-acid oxidation in skeletal muscle in T2DM mice. In addition, HSL and ATGL were significantly activated during triglyceride mobilization in WAT triggered by central nesfatin-1 administration. Adrenergic blockade and morphological denervation of the sciatic and femoral nerves reduced these changes. Taken together, these data suggest that central nesfatin-1 regulates peripheral lipid metabolism in type 2 diabetes via the sympathetic nervous system.
Substances chimiques
Fatty Acids
0
Nucb2 protein, mouse
0
Nucleobindins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
454-464Subventions
Organisme : National Natural Science Foundation of China
ID : 31872791
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2019MC046
Informations de copyright
© 2020 International Union of Biochemistry and Molecular Biology.
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