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Liraglutide improves insulin sensitivity in diabetic mice through reduction of inflammation and induction of thermogenesis.
Author(s) -
Zhou Joseph,
Poudel Anil,
Li Lixin
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb159
Subject(s) - liraglutide , endocrinology , medicine , uncoupling protein , ampk , mitochondrial biogenesis , type 2 diabetes , insulin , brown adipose tissue , thermogenesis , adipose tissue , protein kinase a , thermogenin , biology , chemistry , diabetes mellitus , mitochondrion , kinase , biochemistry
Glucagon like peptide ‐1 (GLP‐1) is released from the ileal mucosa L cells after food digestion to promote glucose stimulated insulin secretion. Liraglutide, a full agonist of the GLP‐1 receptor, has been known to reduce body weight in obese subjects and patients with type 2 diabetes. However, the underlying mechanisms of this effect remains unclear. Mice were fed with high fat high sucrose diet for 3 months to induce diabetes. Two groups of diabetic mice were injected with liraglutide or vehicle daily for 14 days. Improved glycemic control and intra‐peritoneal glucose tolerance test were observed in liraglutide treated group after 14 days. In addition, liraglutide treatment group showed significant reduction of liver weight in association with reduced expression of the phosphorylated Acetyl‐CoA carboxylase‐2 (ACC2) and upregulation of LCAD, cAMP‐activated protein kinase (AMPK)‐α as well as Sirt‐1 in liver and perigonadal fat. The elevation of fatty acid oxidation induced by liraglutide might be mediated through AMPKα‐SIRT‐1 cell signaling pathway. Brown adipose tissue (BAT) plays a key role in regulating energy balance via uncoupling of mitochondria ATP synthesis in rodents. Liraglutide induced BAT differentiation in skeletal muscle, including induction of the uncoupling protein‐1 (UCP‐1), a brown fat specific marker, PR domain‐containing 16 (PRDM16) protein expression, a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. Mitochondrial biogenesis and functional gene such as PPAR‐γ, PGC‐1αand SIRT‐1 were also upregulated by liraglutide in insulin sensitive tissues. Lastly, liraglutide displayed anti‐inflammatory effect. Liraglutide treatment leads to a significantly reduction of circulating IL‐6 as well as IL‐6 content in liver. Expression of iNOS‐1 and COX2 in insulin sensitive tissues were also reduced followed liraglutide treatment. Taken together, our study indicates liraglutide improves insulin sensitivity through multiple pathways which includes suppression of food intake, reduction of inflammation, elevation of fatty acid oxidation and induction of thermogenesis. Support or Funding Information Start Up Fund ( Central Michigan University) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .