Liraglutide reduces lipogenetic signals in visceral adipose of db/db mice with AMPK activation and Akt suppression

Drug Des Devel Ther. 2015 Feb 18:9:1177-84. doi: 10.2147/DDDT.S79175. eCollection 2015.

Abstract

Liraglutide, a glucagon-like peptide-1 analog, has been proved to reduce body weight and visceral adipose tissue (VAT) in human studies. In this study, we aimed at examining lipogenetic signal changes in VAT after weight-loss with liraglutide in db/db mice. The mice were divided into two groups: liraglutide-treated group (n=14, 8-week-old, fasting glucose. >10 mmol/L, liraglutide 300 μg/kg twice a day for 4 weeks) and control group (n=14, saline). We found body weight gain and food intake were reduced after liraglutide treatment (P<0.05). Compared to the control group, the VAT weights were significantly lower in the treated group (2.32±0.37 g versus 3.20±0.30 g, P<0.01) than that in control group. In VAT, compared with control group, the lipogenetic transcription factors PPARγ and C/EBPα expressions were both reduced with pAMPK and pACC increased 3.5-fold and 2.31-fold respectively, while pAkt and pP38MAPK were reduced 0.38-fold and 0.62-fold respectively (P<0.01). In conclusion, VAT was reduced after weight loss with AMPK activation and Akt suppression with liraglutide treatment, which was associated with reduction of lipogenetic process in VAT.

Keywords: AMP-activated protein kinase; lipogenesis; liraglutide; visceral adipose tissue.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Enzyme Activation / drug effects
  • Injections, Subcutaneous
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / metabolism
  • Lipids / antagonists & inhibitors*
  • Lipids / biosynthesis
  • Liraglutide / administration & dosage
  • Liraglutide / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Structure-Activity Relationship

Substances

  • Lipids
  • Liraglutide
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases