The Roles And Significances Of Obestatin In The Regulation Of Feeding Behaviour And Energy Balance

Objective: To study the effects of changes of feeding behaviour (including different times of fasting and refeeding) on the expression of Obestatin in stomach and hypothalamic arcuate nucleus (ARC) of mice. The roles of Obestatin on the regulation of food intake were investigated. Meanwhile, to investigate changes of circulating Obestatin levels and their roles in the regulation of energy balance in the obestity.Methods:1. Experimental research: 50 Kunming white male mice were fed after 1 week adaptively, who were randomly divided into 5 groups.Group A : fasted for 0 h; Group B: fasted for 24 h; Group C: fasted for 48 h; Group D: fasted for 72 h ; Group E: refed for 4 h after fasted for 72 h, each group had 10 cases. Obeserved the changes of the body weight in each group on different times of fasting and refeeding; stomach tissues and brain were kept , the expression of Obestatin in the stomach and ARC were studied by the technique of immunohistochemistry.2. Clinical research: Obeserved 128 cases in the out-patient clinic,ward and medical examination center in our hospital,including 35 normal controls, 93 obesities, comprised by 46 normal glycometabolism cases and 47 glycometabolism abnormalities (including type 2 diabetes and impaired glucose tolerance patients) . Plasma Obestatin, Ghrelin and C reactive protein (CRP) levels were measured by enzyme linked immunosorbent assay (ELISA). Fasting plasma insulin (FPI) levels were measured by radioimmunoassay(RIA). The relationships between plasma Obestatin levels and BMI, HOMA-IR, FPG, FPI levels were also analyzed .Results:1. Experimental results:1.1 The effects of fasting and refeeding on the body weightBody weight in five groups of mouse in the beginning of fasting showed no significant difference. Compared with the body weight in the fasted 0 h group, after fasted for 24 h,48 h,72 h, the body weight were significantly reduced, and increased after refeeding 4 h ( P<0.05).1.2 The effects of fasting and refeeding on the expressions of Obestatin in the stomachCompared with group A ,the expressions of Obestatin in the stomach in B to E groups were significantly reduced (P<0.05), the expressions of Obestatin in E group were slightly increased, but showed no significant difference. The Obestatin expressions during the B,C,D groups showed no significant difference.1.3 The effects of fasting and refeeding on the expressions of Obestatin in the ARCThe Obestatin expressions during the B to E groups showed significant difference (P<0.01). Compared with group A , the expressions of Obestatin in the ARC in B to E groups were significantly reduced (P<0.05). Compared with D group,the expression of Obestatin in E group were slightly increased (P> 0.05). Expressions of Obestatin in the ARC show a downtrend from A to D groups ,but there showed no significant difference during the B,C,D groups (P> 0.05). 1.4 The analysis of associativity of Obestatin in the stomach and ARC Expressions of Obestatin in the ARC correlated positively with the died body weights and expressions of Obestatin in the stomach (r=0.324, 0.346; P=0.022, 0.014), and there were significant negative correlations with the variation of body weight.2. Clinical results:2.1 Comparing the general characters in three groupsCompared with normal control group, BMI,WHR,SBP,DBP,FPG,2hPG,FPI,TG,HOMA-IR,LDL-C,CRP in the obesity group were significantly increased , and HDL-C were reduced (P<0.05).Compared with obesity with normal glycometabolism group, WHR,SBP,DBP,FPG,2hPG,FPI,TG,HOMA-IR,CRP in the obesity with glycometabolism abnormalities group were significantly increased, LDL-C were reduced (P<0.05).2.2 Comparing the levels of Ghrelin and Obestatin in three groupsCompared with normal contrlo group, the levels of Ghrelin and Obestatin in obesity group were significantly reduced (P<0.05), there were no significant difference in the G/O ratio in two groups.Compared with obesity with normal glycometabolism group, the levels of Ghrelin and Obestatin in the obesity with glycometabolism abnormalities group were significantly reduced, G/O ratio were increased(P<0.05).2.3 The analysis of associativity of Obestatin and G/O ratio with other parametersObestatin correlated negatively with BMI, WHR, SBP, DBP, HOMA-IR, FPI, FPG, 2hPG , TG, CRP, there were no significant correlations between G/O ratio with BMI,WHR, SBP, DBP, HOMA-IR, FPI, FPG, 2hPG , TG, CRP. In a multiple regression analysis, BMI and FPG were independently associated with plasma Obestatin levels (b= - 0.048 , - 0.181; P= 0.020 ,0.046 ). In a multiple regression analysis, BMI and FPG were independently associated with plasma Obestatin levels (b= - 0.048 ,- 0.181; P= 0.020 ,0.046 ).Conclusion:1. Obestatin is highly expressed in the stomach and ARC.2. Obestatin in the stomach and ARC changed on the condition of fasting and refeeding, it showed Obestatin may participate in the regulation of feeding behavior ,supposed that the reducing of Obestatin expression might be involved in maintain of energy balance.3. Plasma Obestatin in obesity were significantly reduced than the normal control, Obestatin play an important role in the development of obesity.4. HOMA-IR showed a uptrend alongwith the decrease of Obestatin.The decrease of circulating Obestatin may be involved in the development of abnormal glucose metabolism.5. Obestatin correlated negatively with CRP, Obestatin might be involved in the development of inflammation reaction.