The Preventive Effect Of Paranoxsides Rb1 On Diet-induced Obese C57/BL6 Mice And Its Mechanism

AimsObesity is a major predisposing factor for cancer, type II diabetes, hypertension and coronary heart diseases with their enormous costs both socially and financially. Therefore, there is a pressing demand to research the mechanism of obesity so that effective treatment regimes to deal with its rising prevalence may be devised. It is well believed that energy accumulation can lead to obesity, and the high-fat and high-energy food can especially easily complete the task. However, in both rodents and humans, some become obese while others remain lean when raised the same high-fat and high-energy diet. The previous work has shown that when C57/BL6 mice are fed a high fat diet some mice develop obesity whist others remain lean. This has also been shown in early studies in rats fed a palatable high fat/high sugar diet. The study on this point has showed interesting results on their difference on appetite control system. In the central neural regulatory systems, neuropeptide Y plays an important role in appetite and energy balance. NPY consists of 36 ami no acids, and is a powerful neurochemical stimulator in feeding. PYY is a member of the pancreatic polypeptide family whose structure and function is related to NPY. PYY is mainly secreted from the endocrine L cells of the gastrointestinal tract and is related into the blood stream in response to the ingestion of food, especially fat. PYY has a high affinity for Y2 receptors, and upon binding can inhibit food intake via the hypothalamic arcuate nucleus.Ginsenosides, the main component of Panax ginseng root, has been reported to show several pharmacological actions on the peripheral Metabolism of glucose and lipid and on endocrine secretion. Recent studies showed that administration of Panaxoside Rbl in high fat diet group reduced the body weight, total food intake, fat content, serum ieptin and NO to a level equal or below the normal diet group in SD rats. In vitro study revealed that Rbl promoted adipogenesis in 3T3-L1 cells by enhancing PPARγ2 and C/EBPαgene expression. Little is known about the specific effect and feature of Rbl on anti-obesity in DIO and DR mice, especially compared with diet pattern change, as well as its effect with time change. Besides, the literature revealed that Rbl was a suppressor in central modulation of feeding in the rat through NPY pathways. Our study aimed to find the change of peripheral NPY and PYY between groups.Ginsenoside Rbl, the main component of ginsenosides, have been reported to show a variety of efficacies such as anticancer, antihypertension, antidiabetes, and antinociception. In the present study, the anti-obesity effect of Ginseng Panaxosides Rb1 on diet-induced obese mice were evaluated.MethodsSeventy C57/BL6 male mice were randomly divided into chow diet (N, n=8) group and high fat diet group (n=62). After fed with high fat and energy diet for 12 weeks, the mice were divided into two groups, including an obesity group (DIO, n=20) and obesity-resistant group (DR, n=10) according to the highest and lowest weight gain, with other mice discarded. Obesity group was then subgrouped into DIO-Rb1 injection group (n=10), diet change to normal group (DC,n=5) and no intervention group (HF,n=5). Intraperitoneal injection of Rb-1 was received daily by mice in DIO-Rb1 and DR group for 3 weeks. Body weight and food intake were observed, and fasting blood glucose, lipids was examined by biochemical analyzer. In addition, we also determined the secretion and expression of neuropeptide Y (NPY), Y2 receptor, and Peptide YY (PYY) by enzyme linked immunosorbent assay (ELISA) and real-time RT-PCR.ResultsEffects of Rbl on the body weight and food intakeBody weight is a gold standard of obese. So we firstly investigated the effect of Rbl on body weight of obese mice. After fed with high-fat diet for 12 weeks, the body weight of diet-induced obese (DIO) mice was significant increase. However, after treatment with Rb1 for 3 weeks, the body weight of DIO-Rb1 group was obvious decrease when compared with that in DIO group. In addition, we also detected the food intake after treatment with Rb1. We found that food intake was also decrease in DIO-Rbl group as compared with that in DIO group.Effects of Rbl on the blood glucose and lipidsThe blood glucose and lipids are also important indices of obese. Thus, we also detected the effects of Rb1 on fasting blood glucose and lipids. After fed with high-fat diet for 12 weeks, the fasting blood glucose and total cholesterol (TC) of DIO mice were significant increase. Whereas, after treatment with Rb1 for 3 weeks, the fasting blood glucose and total cholesterol of DIO-Rb1 group were obvious decrease when compared with those in DIO group. Additionally, there was no significant difference in triglyceride(TG) among three groups.Effects of Rb1 on the serum levels of PYY and NPYIt is well known that PYY and NPY are involved in the obese, so we next measured the serum levels of PYY and NPY to explore the possible action mechanisms of Rb1. As shown in table 4, after fed with high-fat diet for 12 weeks, the serum PYY of DIO mice was significant decrease. Rb1 could inhibit the decreasing of serum PYY of DIO mice. On the contrary, after fed with high-fat diet for 12 weeks, the serum NPY of DIO mice was significant increase. Rb1 could reverse the increasing of serum NPY of DIO mice.Effects of Rb1 on the mRNA levels of NPY, NPY-2R and PYYThe mRNA levels of NPY in hypothalamus were significantly lower in N and DIO-Rb1 groups than that in DIO group (P<0.05). Similar pattern was observed in NPY-2R level. Rb1 could reverse the increasing of NPY-2R expression to normal level. The mRNA level of PYY in intestine tract in DIO group was lower than that in any other groupConclusionsTaken together, our results indicate that the ginsenoside Rb1 may be useful in the treatment of obesity via modifying the serum content and mRNA expression of NPY, Y2 receptor and PYY.