Effects of glycyrrhizic acid on peroxisome proliferator-activated receptor γ, lipoprotein lipase and 11β-hydroxysteroid dehydrogenase in rats
thesisposted on 13.01.2017, 04:29 by Chia, Yoke Yin
The metabolic syndrome is a cluster of metabolic abnormalities comprising of dyslipidaemia and insulin resistance (IR). Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor with a pivotal role in adipocyte differentiation and insulin sensitization. Studies on the ligand binding potential of glycyrrhizic acid (GA), a potential agonist to PPARγ displayed encouraging results in the amelioration of metabolic syndrome. Two isoforms of 11β-hydroxysteroid dehydrogenases, namely 11β-HSD1 and 11β-HSD2, regulate intracellular glucocorticoid levels. Lipoprotein lipase (LPL), a regulator of lipoprotein metabolism, is a downstream gene of PPARγ and its expression is reduced with the occurrence of IR and increased activities of 11β-HSD. The effects of two different routes of GA administration (oral vs. intraperitoneal), different dosages of GA and treatment periods were studied in rats. It was found that oral administration of 100 mg/kg GA led to optimum improvements in all the studied parameters. GA treatment led to an overall significant decrease in blood glucose and HOMA-IR (P < 0.05) as well as serum insulin levels (P > 0.05) and improvements in the lipid profile with a decrease in serum TAG, total cholesterol and LDL-cholesterol accompanied by an increase in HDL-cholesterol (P > 0.05). Expression levels of total PPARγ, PPARγ1, PPARγ2 and LPL as well as 11β-HSD1 and 2 activities were measured in six different tissues, i.e., the subcutaneous and visceral adipose tissues, abdominal muscle, quadriceps femoris, liver and kidney. Oral administration of 100 mg/kg GA led to significant increases in the expression levels of total PPARγ, PPARγ1, PPARγ2 and LPL in the subcutaneous and visceral adipose tissues, abdominal muscle and quadriceps femoris (P < 0.05) while non-significant increases (i.e., P > 0.05) were observed in the liver and kidney. The increase in tissue LPL expression correlated with the improvement of lipid profile in the GA-administered rats. GA administration also led to significant decreases (P < 0.05) in 11β-HSD1 activity in all the studied tissues except for the subcutaneous adipose tissue while 11β-HSD2 activity was significantly decreased in all the six tissues examined (P < 0.05). Overall, this study has shown that GA can possibly be used to ameliorate metabolic syndrome and demonstrated the interlinking roles of PPARγ, 11β-HSD and LPL in glucose homeostasis and lipid metabolism.