Liraglutide regulates lipid metabolism via FGF21- LKB1- AMPK- ACC1 pathway in white adipose tissues and macrophage of type 2 diabetic mice.
Biochem Biophys Res Commun
; 548: 120-126, 2021 04 09.
Article
em En
| MEDLINE
| ID: mdl-33640604
ABSTRACT
Liraglutide (LRG), a glucagon-like peptide 1 analogue (GLP1A), could decrease body mass of type 2 diabetes (T2DM), but the exact molecular mechanism of LRG has not been elucidated. This study was performed to explore whether LRG regulated TG synthesis via secretion of FGF21 and modulating AMP-dependent protein kinase (AMPK) pathway in an autocrine mode. Two-month-old male C57BL/6 mice were fed high-fat diet (HFD) for 4 months followed by injection of 30 mg/kg streptozotocin (STZ) to induce state of T2DM. Then DM mice were given LRG (0.4 mg/kg/d) for 4 months. Body mass, serum lipids and FGF21 levels, related gene expression were analyzed. Lipopolysaccharide (LPS)-induced RAW264.7 cells were treated with palmitic acid and different concentrations of LRG. Then Exendin (9-39), siRNA targeted to liver kinase B1 (LKB1) and Compound C were used to confirm the signaling pathway. LRG decreased adipocyte size, increased secretion of FGF21, and promoted phosphorylation of LKB1, AMPK and Acetyl coenzyme A carboxylase 1 (ACC1) in white adipose tissue (WAT) of DM mice. LRG also increased phosphorylation of fibroblast growth factor receptor 3 (FGFR3), LKB1, AMPK and ACC1 via FGF21 secretion, which ultimately inhibited synthesis of TG in macrophage. In conclusion, FGF21 is induced to be expressed in macrophage by LRG, which then activates LKB1-AMPK-ACC1 pathway in an autocrine manner.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetil-CoA Carboxilase
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Proteínas Serina-Treonina Quinases
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Diabetes Mellitus Tipo 2
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Metabolismo dos Lipídeos
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Tecido Adiposo Branco
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Proteínas Quinases Ativadas por AMP
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Fatores de Crescimento de Fibroblastos
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Liraglutida
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Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article