Glycyrrhiza glabra L. leaf extract ameliorates palmitic acid-induced hypertrophy and insulin resistance in 3T3-L1 murine adipocytes

Background Obesity, one of the most common public health diseases, is a metabolic disorder correlated with increased risk of numerous pathologies, such as cardiovascular diseases, dyslipidemia, and type 2 diabetes. It is associated with free fatty acids (FFAs) accumulation and alteration of adipokine levels, which promote lipotoxicity and induce the onset of a hypertrophic condition and an insulin resistance state in adipose tissue. In vitro and in vivo studies have reported that Liquorice (Glycyrrhiza glabra L., family Leguminosae), one of the most popular medicinal plants known worldwide, is able to reduce the development of obesity and related diseases. Traditionally only the roots of this plant have been examined for their beneficial effects, while scarce attention has been dedicated to liquorice aerial parts, always considered a waste product, but known to contain a large amount of bioactive components, including inositols and dihydrostilbenes, able to exert anti-inflammatory and antioxidant effects, and to act like an insulin sensitizing agent. Thus, in this study we evaluated the in vitro potential beneficial effects of a G. glabra leaves methanolic extract (GGLME) against hypertrophy and insulin resistance, induced by high concentrations of the FFA palmitic acid (PA), in 3T3-L1 murine adipocytes. Methods In all experiments, fully differentiated 3T3-L1 adipocytes were pretreated with different concentrations of GGLME (40-80 μg/mL) for 24 h, and then exposed to high concentrations of PA (1 mM) for further 24 h to induce lipotoxicity and therefore adipocyte hypertrophy in adipose tissue. To evaluate the insulin resistance condition, cells were then treated with 100 nM insulin for 15 min. The effects of the extract on lipid accumulation have been evaluated through the histological technique of Oil Red O staining, whereas the main markers of insulin resistance were evaluated by Western blot. Results The results obtained demonstrate that GGLME pretreatment protects 3T3-L1 adipocytes from PA-induced hypertrophy through inhibition of the adipogenesis process, as shown by the reduced lipid accumulation in Oil Red O staining assay. In addition, our results demonstrate that PA-induced lipotoxicity determines the onset of insulin resistance in 3T3-L1, inducing an impairment of insulin modulated PI3K/Akt/GLUT1 axis. Interestingly, extract pretreatment was able to effectively reverse the effects of PA in a dose-dependent way. Conclusions These findings clarify the molecular mechanisms underlying the protective effect of the methanolic extract of liquorice leaves against a hypertrophic and insulin resistance state, induced by PA, in adipose tissue. These observations allow us to hypothesize, hence, a possible application for this product, considered a vegetable waste, as a new source of bioactive compounds useful in the prevention of pathological conditions linked to obesity.