| BackgroundMost people with type2diabetes are overweight or obese, which furtherincreases cardiovascular risk of these subjects and make treatment a troublesome andcomplicated problem. Glucagonlike peptide-1(GLP-1) is regarded as the most curableand promoted drug to obese type2diabetes for its delay of disturbances in β-cellfunction,enhancement of insulin secretion,weight loss,improvement of endothelialcell function and reduction cardiovascular risk. Exendin-4(Ex-4) developed as aGLP-1receptor agonists for the past few years, which have a demonstrated effect onweight loss and suppression of appetite,but the exact mechanism is not yet clear.It issupposed that central nervous system the feeding signal of the hypothalamus inparticular is involved.Some studies demonstrated that the decreased food intake byEx-4is caused by activating the GLP-1receptor signaling pathways of thehypothalamic aruate nucleus (ARC) and paraventricular nucleus (PVN), whichsuggests that Ex-4can improve body weight and blood glucose control by modifyingthe function of hypothalamus in obese type2diabetics.However,there is little reportabout how to evaluate the impact of Ex-4on hypothalamic function in clinicalpractice. In the recent years, functional magnetic resonance imaging (fMRI) is widelyused as an important tool in evaluating feeding function of the hypothalamus.AndBlood oxygenation level dependent（BOLD）imaging is the major technique used inthis field,but the signal changes associated to activation detected by BODL imagingare thought to occur less close-temporally and spatially to the activated areas thandiffusion changes associated to activation by another two techniques ofdiffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI),which basedon the diffusion behavior of water molecules in biological tissues.However,under thecircumstance of low b values (b<1000s/mm2),conventional DWI signal is so easilyaffected by microcirculatory blood flow that it does not reflect the puremoleculardiffusion of water, which decrease the diagnostic sensitivity and specificity.Biexponential model based functional diffusion weighted imaging(fDWI) allow thecalculation of pure molecular-based real diffusion coefficient(D value) and the tissuemicrovascular perfusion,thus obtain a more accurate information about activatedsignal.In a word,fDWI technique might be a new diagnosing approach for the direct,non-invasive evaluation for the hypothalamus functional imaging research.ObjectiveTo observe the effects of Ex-4intervention on the change of feeding behavior,the feedingsignal intensity of hypothalamic fDWIin obese diabetic rats,and toinvestigate the possible relationship between them,and hope tolay the foundation forfurther evaluation of the mechanism of Ex-4in the regulation of hypothalamic feedingsignal.Subjects and methodsArandomized,controlledstudywas conducted,46rats wererandomly divided into5groups, which were obese type2diabetes(O2D), obese none-diabetes(ON2D),none-obese type2diabetes(NO2D), none-obese none-diabetes(NON2D) and normal diet(ND)respectively.Each group of rats were undertaken2.5ug/kg Ex-4intervention,and then to investigate the change of their food intakeat-5min,5min,35min,65min,95min and125minbefore or after Ex-4injection respectively.The hypothalamicfDWI scanning operation was as followed in the same5time to observe the signalintensity change of feeding center, and theactual diffusion coefficient (D values) ofhypothalamusamong five groups were compared respectively.Linear correlationanalysiswas usedto analyze thecorrelation between D valueand food intake ofrats.Statistical software of SPSS17.0for statistics was used, and P<0.05wasconsidered being significantly difference.Results1. Baseline hypothalamicfDWI differences among four groups in fasting statuswere statistically significant (F=3.57, P=0.047).The baseline D values of groupON2D, group NO2D and groupNON2Dwere higher than that of group O2D,respectively (P<0.05)，and no difference was detected bwteen group NON2D andND(P=0.790).2. Food intake comparison before Ex-4intervention showed thatthere was nodifference among fivegroups at-5min afterEx-4injection (F=1.338, P=0.322).Therewas no differenceof food intake between the five time point(5min,35min,65min,95min and125min) and-5min afterEx-4injectionin groupO2D,NO2D and NDrespectively (P>0.05, respectively). No difference was also found at5min,35min,65min and125min compared to-5min afterEx-4injection in group ON2D (P>0.05),yeta slightly reduction of food intake was found at95min compared to-5min(P=0.053).In group NON2D, reduction of food intake at35min was found compared to-5min (t=5.284，P=0.034), and nodifference was found at5min,65min,95min and125min compared to-5min (P>0.05).3.Comparison of D value showed that there was no differenceof five time point(5min,35min,65min,95min and125min) in groupO2D,NO2D and ND comparedto-5min respectively (P>0.05,respectively).Lower level of D value at35min,65min,95min and125min were found compared to-5min after Ex-4injection in groupON2D(P<0.05).In group NON2D,lower level of D values were found at35min,65mincompared to that of-5min respectively(P<0.05, respectively)4. Comparison of food intake showed that food intake of ratsat-5minwerenosignificant difference (F=1.436, P=0.303)among five groups, andno significantdifferencewas foundat5min，35min,65min and125min after EX-4injectioncompared to-5min (p>0.05).But a slightly reduce (F=2.645,P=0.097) of food intakewas found at95min compare to5min, in whichgroup ON2Dthat was lower thangroupO2D(P=0.036), group ON2Dthat was slightly lower thangroup NON2D(P=0.052),and group ON2Dthat was lower thangroup NO2D(P=0.013).5.D value comparisonshowed that there was no differenceat5minafter Ex-4injection among four groups(t=0.654, P=0.637), yet significantly lower level of Dvalues were found at35min,65min,95min and125min respectively compare to-5min(P<0.05,respectively).Paired wise comparison showed thatgroup ON2D wasdetectedlower level of D values than that of group O2D, group NO2D, group NON2D and NDrespectively (P<0.05, respectively), whereas no difference was found between groupO2D and NO2D, group O2D and NON2D respectively (P>0.05, respectively).6. Linear correlation analysis showed that positive correlation were foundbetween food intake (of5min,35min,65min,95min and125min after Ex-4injection)infive groupsand D values ofcorresponding time points, and the related coefficientswere RO2D=0.557，RON2D=0.628，RNO2D=0.608，RNON2D=0.616,RND=0.479, respectively.Conclusions1. The hypothalamic fDWI signal intensityof obese type2diabetic rats wasweakened compared with obese none-diabetic, none-obesediabetic and none-obese non-diabetic rats respectively, suggesting that coexistence of obesity and type2diabetes mightfurther affect the signal release of hypothalamus feeding center.2. Ex-4intervention would significantly inhibit theearlystage of food intakeofobese type2diabetic rats, which beingconsistency withtheir ownhypothalamicfDWI signal changes, but subsequent feeding behavior and hypothalamic fDWI signalchange only affected by obesity or not, it’s not clear that if the presence of diabetesplaying a role in the change of feeding behavior and hypothalamic signal intensity. |
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