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


CONCLUSIONS
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.
Eu
Chia Hui Apphia
CH
School of Science, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway 46150, Selangor Darul Ehsan, Malaysia.
Lim
Wai Yen Alfred
WY
Ton
So Ha
SH
bin Abdul Kadir
Khalid
K
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D004041:Dietary Fats / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006706:Homeostasis / Q000187:drug effects; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D008055:Lipids; D012333:RNA, Messenger; D019695:Glycyrrhizic Acid; D008071:Lipoprotein Lipase