Liraglutide induces beige fat development and promotes mitochondrial function in diet induced obesity mice partially through AMPK-SIRT-1-PGC1-α cell signaling pathway.
PURPOSE
Glucagon like peptide-1 (GLP-1) is produced to induce postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, has a protective effect on weight gain in obese subjects. Brown adipose tissue plays a major role in the control of energy balance and is known to be involved in the weight loss regulated by liraglutide. The putative anti-obesity properties of liraglutide and the cell signaling pathways involved were examined.


METHODS
Four groups of C57/BL6 mice fed with chow or HFHS diet were injected with either liraglutide or vehicle for four weeks. Western blotting was used to analyze protein expression.


RESULTS
Liraglutide significantly attenuated the weight gain in mice fed with HFHS diet and was associated with significant reductions of epididymal fat and inguinal fat mass. Furthermore, liraglutide significantly upregulated the expression of brown adipose-specific markers in perigonadal fat in association with upregulation of AMPK-SIRT-1-PGC1-α cell signaling. However, elevation of brown fat markers in skeletal muscle was only observed in HFHS diet fed mice after liraglutide treatment, and AMPK-SIRT-1 cell signaling is not involved in this process.


CONCLUSIONS
the anti-obesity effect of liraglutide occurs through adaptive thermogenesis and may act through different cell signaling pathways in fat and skeletal muscle tissue. Liraglutide induces beige fat development partially through the AMPK-SIRT-1-PGC1-α cell signaling pathway. Therefore, liraglutide is a potential medication for obesity prevention and in targeting pre-diabetics.
['Zhou|Joseph|J|', 'Poudel|Anil|A|', 'Chandramani-Shivalingappa|Prashanth|P|', 'Xu|Biao|B|', 'Welchko|Ryan|R|', 'Li|Lixin|L|0000-0003-3016-4228']
D000263:Adenylate Kinase D000069796:Adipose Tissue, Beige D050154:Adiposity D000818:Animals D059305:Diet, High-Fat D007004:Hypoglycemic Agents D050155:Lipogenesis D000069450:Liraglutide D008297:Male D051379:Mice D008928:Mitochondria D009765:Obesity D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha D015398:Signal Transduction D056564:Sirtuin 1
Liraglutide Beige fat Diet induced obesity Insulin resistance