Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

Abstract

Background: The metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL), an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR). Glycyrrhizic acid (GA), a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state.

Results: Oral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.05). LPL expression was up-regulated in the kidney, heart, quadriceps femoris, abdominal muscle and the visceral and subcutaneous adipose tissues but down-regulated in the liver--a condition in reverse to that seen in high-fat diet-induced obese rats without GA. With regard to lipid metabolism, GA administration led to significant hypotriglyceridemic and HDL-raising effects (p < 0.05), with a consistent reduction in serum free fatty acid, total cholesterol and LDL cholesterol and significant decrease in tissue lipid deposition across all studied tissue (p < 0.01).

Conclusion: In conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA.

Figure 1

Relative LPL expression of Group B compared to A. Fold difference of LPL expression in tissues studied, using β-actin (BAC) as the endogenous reference, tissues of rats from group A as the calibrator and tissues of rats from group B as the target. LPL expression was down-regulated in all tissues except the liver. [Group A: rats fed on normal diet without GA; Group B: rats fed on high-fat diet without GA].

Figure 2

Relative LPL expression of Group C compared to B. Fold difference of LPL expression in tissues studied, using BAC as the endogenous reference, tissues of rats from group B as the calibrator and tissues of rats from group C as the target. LPL expression was up-regulated in all tissues except the liver. [Group B: rats fed on high-fat diet without GA; Group C: rats fed on high-fat diet and given 100 mg/kg of GA].

Figure 3

Comparison of blood glucose. Mean concentration of blood glucose (mmol/L) of rats from groups A, B and C. * indicates p < 0.05 when compared between groups. [Group A: rats fed on normal diet without GA; Group B: rats fed on high-fat diet without GA; Group C: rats fed on high-fat diet and given 100 mg/kg of GA].

Figure 4

Comparison of serum insulin. Mean concentration of serum insulin (ng/mL) of rats from groups A, B and C. * indicates p < 0.05 when compared between groups. [Group A: rats fed on normal diet without GA; Group B: rats fed on high-fat diet without GA; Group C: rats fed on high-fat diet and given 100 mg/kg of GA].

Figure 5

Comparison of HOMA-IR. Mean HOMA-IR of rats from groups A, B and C. ** indicates p < 0.01 and * indicates p < 0.05 when compared between groups. [Group A: rats fed on normal diet without GA; Group B: rats fed on high-fat diet without GA; Group C: rats fed on high-fat diet and given 100 mg/kg of GA].

Figure 6

Comparison of serum lipid. Mean concentration of total cholesterol, TAG, HDL-cholesterol, LDL-cholesterol and serum FFA in rats from groups A, B and C. ** indicates p < 0.01 and * indicates p < 0.05 when compared between groups. [Group A: rats fed on normal diet without GA; Group B: rats fed on high-fat diet without GA; Group C: rats fed on high-fat diet and given 100 mg/kg of GA].

Figure 7

Comparison of tissue lipid deposition. Lipid deposition in tissues studied, measured in arbitrary units (AU). Sections of VAT and SAT were used as positive controls. ** indicates significant increase in lipid deposition when comparing between Group A with each of Groups B and C, and a significant decrease in lipid deposition in Group C compared to B (p < 0.01). [Group A: rats fed on normal diet without GA; Group B: rats fed on high-fat diet without GA; Group C: rats fed on high-fat diet and given 100 mg/kg of GA].