Inhibitory Effect Of Naringin And Naringenin On Pancreatic Lipase And Its Anti-obesity Effect In Rats

Obesity is one of the most common nutritional dilemmas in modern countries.It is considered to be a potential risk factor leading to the development of a large number of devastating diseases.One of the effective ways to treat obesity caused by diet is to find effective metabolic enzyme inhibitors,such as pancreatic lipase（PL）,which can prevent fat absorption and digestion.In recent years,natural products have attracted more and more attention in the treatment of obesity because of their minimal side effects,which can prevent or reduce the risk of chronic diseases.This study confirmed the inhibitory effect and mechanism of naringin or naringenin on PL activity in vitro,and its anti-obesity effect on high fat diet（HFD）rats.In vitro enzymatic experiments showed that the IC₅₀corresponding to the inhibitory effect of naringin or naringenin on PL were 6.92±0.12 mmol/L and 2.413±0.05 mmol/L respectively,and both inhibited PL activity in a reversible competitive manner.Fluorescence spectrum experiments showed that naringin or naringenin interacted with PL to form naringin-PL complex or naringenin-PL complex.The fluorescence of PL was statically quenched,and the microenvironment around PL was changed（hydrophobicity increased or decreased）,resulting in the decrease of enzyme activity.Naringin or naringenin combined with PL,ΔG<0,ΔS>0 andΔH<0,indicating that the binding is spontaneous and mainly through electrostatic interaction.Fourier transform infrared spectroscopy showed that the combination of naringin or naringenin with PL changed the proportion of secondary structure of the enzyme,the decrease ofα-helix and the stability of the structure,resulting in the decrease of enzyme activity.Molecular docking showed that naringin or naringenin docked with the active site of PL to prevent the binding of substrate to enzyme.Through the acute corn oil tolerance test,naringin or naringenin can reduce the content of triglycerides（TG）in rat serum.In addition,12 week animal intervention study showed that naringin or naringenin inhibited the increase of body weight and organ weight,reduced the concentration of TG and total cholesterol（TC）in serum and liver,and increased the content of high-density lipoproteincholesterol（HDL-C）in serum.Meanwhile,the wet weight of feces and the content of TG in feces of rats treated with naringin and naringenin increased.H&E staining showed that naringin or naringenin could improve the adipocyte hypertrophy and liver degeneration caused by high-fat diet in rats,making both adipocytes and liver tend to normalize.In conclusion,the weight loss effect of naringin or naringenin in rats treated with high-fat diet may be mediated in part by inhibiting PL activity to delay intestinal fat absorption.These findings may provide a theoretical basis for further study of naringin or naringenin as a natural weight loss supplement.