| Obesity is the fifth largest risk factor for death in the world,its development process is extremely complex.It is the early manifestation of many cardiovascular diseases.Inflammatory responses and free fatty acids produced by obesity,proteins specifically expressed in adipose tissue such as PPAR?,etc,adipocytokines ADPN,TNF-?,etc,and sphingomyelin ceramides are all related to obesity-induced insulin resistance(IR)closely related.Currently marketed weight loss products or medicines have large side effects and limited therapeutic effects.Therefore,it is particularly important to find effective natural non-toxic products to treat obesity and explore its possible action pathways and mechanisms.Gooseberry,also known as Lantern Fruit,is rich in amino acids,vitamins,polyphenols,flavonoids and other nutrients,and rich in anthocyanins(Gooseberry anthocyanins,GA).Studies have shown that GA has significant antioxidant,anti-inflammatory and anti-fibrosis effects in mice.In this study,HFD mice model was established by intragastric administration of high-fat emulsion to explore the effect and mechanism of GA on alleviating IR by inhibiting ceramide synthesis.The HFD model was induced by intragastric administration of high fat emulsion to investigate the intervention effect of GA on IR in HFD mice.The effects of GA on liver histomorphology and blood lipids in HFD mice were investigated by body weight,visceral fat,liver index,TC,TG,HDL-C,LDL-C and liver tissue section staining,and the lipid-lowering effect of GA on HFD mice was determined.The effects of GA on oxidative stress in HFD mice was determined by detecting the levels of oxidative stress indexes SOD and GSH-Px;the effect of GA on glucose tolerance in hyperlipidemic mice was determined by glucose tolerance test;the levels of serum insulin,ADPN and the indexes of ISI and HOMA-IR were determined to clarify the effect of GA on improving insulin sensitivity and enhancing insulin sensitivity in HFD mice.The above experiments proved that the HFD mice model was successfully established and produced IR.The results showed that GA significantly alleviated the weight gain of HFD mice from 53.73±2.24 g to49.02±2.23 g,decreased the visceral fat and liver index of HFD mice,reduced the levels of TC,TG,LDL-C and increased the level of HDL-C in mice,alleviated the oxidative stress of mice,and increased the activities of SOD and GSH-Px from69.49 U/m L and 96.74 U/m L to 105.86 U/m L and 117.07 U/m L.Increased the glucose tolerance of mice,improve the ISI and IR,ISI level from-5.15 to-4.54.HOMA-IR decreased from 6.57 to 5.75.The results of animal experiments showed that GA could alleviated the IR phenomenon of HFD mice to some extent in a dose-dependent manner.The effect of GA on the expression of IL-6 and TNF-? m RNA in HFD mice was detected by Real-time PCR technique,and the expression of S1P/Cer signal pathway in HFD mice was detected by Western Blot method.According to the results of Real-time PCR detection,the m RNA expression of inflammatory factor IL-6,TNF-? was significantly decreased.Western Blot results showed that GA significantly inhibited the activation of Cer S6 in S1P/Cer signaling pathway,inhibited the expression of ceramide downstream protein PKC?,promoted the activation and phosphorylation levels of Akt,significantly increased the expression level of Sph K2 protein,significantly inhibited the expression level of PPAR? and its downstream CD36 proteins.In conclusion,GA can effectively reduce the level of blood lipids in HFD mice,reduce inflammation,enhance insulin sensitivity and alleviate insulin resistance in HFD mice.It can improve IR through S1P/Cer signal pathway.This study provides a scientific theoretical basis for the future study of GA as a natural product to reduce blood lipids and treat IR. |
PDF Full Text Request