2. Academic Validation
  3. Liraglutide regulates lipid metabolism via FGF21- LKB1- AMPK- ACC1 pathway in white adipose tissues and macrophage of type 2 diabetic mice

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. 2021 Apr 9;548:120-126. doi: 10.1016/j.bbrc.2021.02.065.
Nan Zhang 1,  Chao Liu 1,  Yi Zhang 2,  Dongmei Xu 3,  Li Gui 4,  Yunxia Lu 5,  Qiu Zhang 6
Affiliations

Affiliations

  • 1 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 2 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, China.
  • 3 Department of Biochemistry and Molecular Biology, China.
  • 4 The Comprehensive Laboratory, School of Basic Medical Science, Anhui Medical University, Hefei, China.
  • 5 Department of Biochemistry and Molecular Biology, China; The Comprehensive Laboratory, School of Basic Medical Science, Anhui Medical University, Hefei, China. Electronic address: luyunxia@ahmu.edu.cn.
  • 6 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: zhangqiu@ahmu.edu.cn.
PMID: 33640604 DOI: 10.1016/j.bbrc.2021.02.065
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.

Keywords

AMPK; FGF21; FGFR3; Liraglutide; Macrophage; White adipose tissues.

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