Endocrine Abstracts

The Glucagon-like peptide-1 receptor is widely expressed in diverse tissues including the liver. GLP-1 contributes itself to the regulation of glucose homeostasis and has important effects in lipid metabolism even preventing liver steatosis induced by high fat diets.

The aim of this study was to analyse the short-term effects of liraglutide on key enzymes of the hepatic energy metabolism.

Thirty-six Sprague-Dawley young adult male rats were studied (weight range 350–400 g). Control rats were fed ad libitum, while the fast group (F) were deprived of food for 48 hours, and treated with liraglutide (100 μg/Kg/12 h; CT/LIR; F/LIR) or vehicle (CT/VEH; F/VEH) for 48 hours. Rat body weight was measured at 0, 24 and 48 hours. At 48 h, rats were sacrificed and liver samples were collected and stored at −80 °C until analysis. mRNA expression of G6P, PCK-1, DGAT-1, GPAT4, CPT1A and ACACA in the liver were assessed by real time PCR.

CT/LIR rats gained less body weight (−6.4 g/100 g, P<0.0001) than CT/VEH at 24 h and still less at 48 h (−2.9 g/100 g, P<0.0001). The expression levels of G6P and PCK-1, key enzymes in gluconeogenesis, decreases in rats treated with liraglutide by a 58% (P<0.05) and 75% (P<0.01) respectively. On the other hand, DGAT-1 and GPAT4 levels, involved in synthesis of triacylglycerol, were not modified by LIR. In addition, CPT1a and ACACA, enzymes implicated in the synthesis & metabolism of fatty acids, yielded no significant differences. Fasting just increased CPT1 levels (271% F/VEH vs CT/VEH, P<0.01), and LIR treatment reduced them (92% F/LIR, P<0.01 vs F/VEH).

In conclusion, Liraglutide modifies the metabolism of energy substrates in the liver reducing glucose production in normal feeding and CPT1a specially in fasting, limiting lipid access to mitochondria. These metabolic changes may underlie the prevention of liver steatosis attributed to GLP-1 analogues.