Glycyrrhizic acid prevents high calorie diet−induced metabolic aberrations despite the suppression of peroxisome proliferator-activated receptor γ expression

• Rats fed a diet high in fat and sucrose for 4 wk developed metabolic syndrome.
• Glycyrrhizic acid (GA) reduced stress hormone levels and normalized gluconeogenic enzyme activities.
• GA specifically enhanced lipoprotein lipase expression in the cardiac and skeletal muscle tissues.
• Overall, GA supplementation prevented diet-induced metabolic risks.
• The peroxisome proliferator-activated receptor-γ agonistic activity of GA needs to be reexamined.

ObjectiveTo investigate the effects of glycyrrhizic acid supplementation on glucose and lipid metabolism in rodents consuming a high-fat, high-sucrose diet.MethodsTwenty-four male, 8-week old Sprague Dawley rats with an initial weight of 160 to 200 g were randomised into three groups (n = 6 for each group): groups A (standard rat chow), B (high-fat, high-sucrose diet), and C (high-fat, high-sucrose diet + 100 mg/kg/d of glycyrrhizic acid via oral administration). The rats were treated accordingly for 4 wk. Glycaemic parameters, lipid profile, stress hormones, and adiponectin levels were measured after the treatment. Relative gene expressions of peroxisome proliferator-activated receptor α and γ, lipoprotein lipase as well as gluconeogenic enzymatic activities in different tissues were also determined.ResultsConsumption of high-fat, high-sucrose diet triggered hyperglycaemia, insulin resistance, and dyslipidemia, which were effectively attenuated by supplementation with glycyrrhizic acid. Glycyrrhizic acid supplementation also effectively reduced circulating adrenaline, alleviated gluconeogenic enzymes overactivity, and promoted the upregulation of lipoprotein lipase expression in the cardiomyocytes and skeletal muscles. A high calorie diet also triggered hypoadiponectinaemia and suppression of peroxisome proliferator-activated receptor γ expression, which did not improve with glycyrrhizic acid treatment.ConclusionSupplementation with glycyrrhizic acid could alleviate high calorie diet–induced glucose and lipid metabolic dysregulations by reducing circulatory stress hormones, normalizing gluconeogenic enzyme activities, and elevating muscular lipid uptake. The beneficial effects of these bioactivities outweighed the adverse effects caused by diet-induced repression of peroxisome proliferator-activated receptor γ expression, resulting in the maintenance of lipid and glucose homeostasis.