Endocrine Abstracts (2018) 56 P522 | DOI: 10.1530/endoabs.56.P522

GLP-1 increases the availability of substrates and prioritizes the use of lipids in muscle metabolism

Laura Toba, Juan Fandiño, Yolanda Diz-Chaves, Lucas Carmelo Gonzalez-Matías & Federico Mallo

CINBIO, Vigo, Spain.

The skeletal muscle expresses the Glucagon-like Peptide 1 (GLP-1) receptor, although its effects in this tissue are not well known. Muscles are a major sink of energy substrates. The aim of our study was to examine the mid-term effect of Liraglutide (LIRA), a GLP-1 receptor agonist, in the expression of molecular indicators of the metabolic activity of the muscle, which includes enzymes, transporters, and intracellular signals. Twenty young Spague-Dawley male rats (350-400 g) were treated for seven days with LIRA (100 μg/Kg/12 hours / i.p) or vehicle. Body weight and food intake were monitored daily. After the sacrifice, samples of muscle and serum was stored at −80° C. We studied the expression by rtPCR of mRNA for GLUT-4, CD-36, GAPT-1, GAPT-4, Fosfofructo-kinase-1 (FFK-1), CPT-1, UCP-2, PPAR-gamma and mTOR. In addition, we studied serum proteomics by the profile adipokine Array Kit (RD systems, bio-Techne) for rat. Treatment with LIRA, reduces total food intake (kCal) and body weight gain just in the first 24 hr but not afterwards. LIRA treatment increases the mRNA expression of the translocase CD36 (+74%) that facilitates the entry to the cell of fatty acids, and the expression of the glucose transporter GLUT4 (+317%). LIRA also increases the expression of PPARγ (+800%) involved in the biogenesis of mitochondria and UCP2 (+298%) that promote the oxidation of fatty acids to the detriment of pyruvate from glycolysis. LIRA does not modify the phosphofructokinase 1 nor of CPT-1 expression. In addition, it reduces the expression of glycerol-3-phosphate acyltransferase-1 (GAPT 1, −80%), limiting the formation of mitochondria ketone bodies, and mTOR (−70%), determinant in the synthesis of new fibres. The administration of LIRA also reduce total fat mass (g/100g bw) and the serum circulating levels of total triglycerides. In conclusion, LIRA promotes the entry of fatty acids and glucose in muscle, facilitates the production of energy from fatty acids and the biogenesis of mitochondria, all together improving the efficiency of the muscular energy machinery.

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