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Liraglutide Induces Brown Adipocyte Specific Genes in Mice Skeletal Muscle Tissue
Author(s) -
Li Lixin,
Zhou Joseph Yi,
Bahaee Jamsheed
Publication year - 2016
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.30.1_supplement.851.11
Subject(s) - endocrinology , medicine , liraglutide , adipocyte , brown adipose tissue , biology , thermogenin , peroxisome proliferator activated receptor , adipose tissue , fgf21 , receptor , type 2 diabetes , chemistry , diabetes mellitus , fibroblast growth factor
Obesity is a risk factor for type 2 diabetes, coronary artery disease, and stroke. Glucagon like peptide ‐1 (GLP‐1) is synthesized by the L cells of ileal mucosa and is released after nutrients ingestion to potentiate glucose stimulated insulin secretion. Liraglutide, a full agonist of the GLP‐1 receptor (GLP‐R), has long‐lasting effects due to its increased resistance to enzymatic degradation. Clinical data has demonstrated the protective effect of liraglutide on weight gain in type 2 diabetes subjects. However, the underlying mechanisms of this protective effect have not been identified. Brown adipose tissue plays a major role in control of energy balance in rodents, whether GLP‐1 activate brown fat differentiation has not been studied. C2C12 myoblasts are known to be able to differentiate into adipocytes after stimulation. By treating the undifferentiated C2C12 myoblast with 5nM liraglutide, we observed a significant induction of GLP‐1 receptor after 24 h. C2C12 cells were cultured to confluence, and then exposed to brown adipocyte differentiation medium in the presence or absence of 5nM liraglutide, the mRNA level of brown fat enriched genes including peroxisome proliferator‐activated receptor α (PPAR‐α) and cell death activator‐A (Cidea) were upregulated after 6 days of induction of differentiation compare to control cells. Induction of peroxisome proliferator‐activated receptor‐γ coactivator (PGC)‐1α mRNA was observed as early as 3 d post‐induction. In vivo study was performed by injecting C57 black/6 mice with liragludie daily for 5 weeks. Both mRNA and protein levels of uncoupling protein‐1(UCP‐1), a brown fat specific gene, are significantly induced in skeletal muscle tissue after liraglutide treatment. Lirglutide also upregulated other brown fat enriched gene including PGC‐1α, Cidea, and PPAR‐α. Our study indicates that liraglutide induces brown adipogenesis. GLP‐1 and its analogues are potential therapies for obesity and obesity related metabolic disorders. Support or Funding Information Central Michigan University Faculty Startup Fund.