Glycyrrhizic Acid Improves Lipid and Glucose Metabolism in High-Sucrose-Fed Rats

Background: The alarming increase in sugar consumption worldwide has largely contributed towards the escalating symptoms of metabolic syndrome (MetS) such as obesity, insulin resistance and dyslipidaemia. Reduction in lipoprotein lipase (LPL) activity leads to dyslipidaemia, a hallmark of MetS. Increased activation of glucocorticoid receptors also results in symptoms of MetS. Glycyrrhizic acid (GA), a triterpenoid saponin, inhibits 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1), which leads to reduced hexose-6-phosphate (H6PDH) activity and decreased glucocorticoids (GCs) production. GCs induce the gene transcriptions of enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in the gluconeogenic pathway. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state. Methods: Twenty-four male Sparague Dawley rats were randomly divided into three treatment groups (Group A, normal diet; Group B, high-sucrose diet; Group C, high-sucrose diet with 100 mg/kg of GA). After 28 days of treatment, the blood samples collected were analyzed for blood glucose, serum insulin and lipid profiles and the tissues collected were used for LPL expression, 11 beta-HSD1, H6PDH and PEPCK activities analysis. Statistical analysis was done using REST9 and SPSS softwares, P <= 0.05 was considered significant. Results: Oral administration of 100mg/kg GA to high-sucrose induced rats significantly lower blood glucose (32.2%), serum insulin (68.4%), HOMA-IR (81.6%) (P < 0.05) and improved lipid parameters (P < 0.05) with no elevations in blood pressure. LPL activity was upregulated in all tissues (P > 0.05), with significant upregulation in the liver (2 fold) (P < 0.01). 11 beta-HSD activity was lower in all tissues in GA treated rats compared to the group on high-sucrose diet alone (P < 0.05). Smaller elevations in H6PDH activities were observed in the liver (14.2%), kidney (7.17%), subcutaneous adipose tissue (SAT) (15.3%), abdominal muscle (AM) (18.4%) and quadriceps femoris (QF) (15.3%). PEPCK activities were elevated in the liver (14.9%) and kidney (7.0%) (P < 0.05) but increased in the SAT (74.4%) and visceral adipose tissues ( VAT) (142.0%) (P < 0.01). Smaller increases were observed in the hepatic (61.6%) and renal (47.4%) G6Pase activities (P < 0.05). Conclusions: High-sucrose feeding induced hypertension, hyper-glycemia, insulin resistance and dyslipidemia. GA could ameliorate these symptoms by regulating the glucose and lipid metabolism through 11 beta-HSD1 inhibition and possibly PPAR gamma agonism. GA induced LPL expression and contributed towards a postive shift in the lipid profiles. GA also prevented hyperglycaemia and improved insulin sensitivity in the high-sucrose fed rats without causing hypertension. Thus, GA appears to be a possible therapeutic compound in lowering the risks of developing dyslipidaemia and possibly T2DM.