The Effect Of Orexin-A On Food Intake And Body Weight Of Obese Rats Induced By High-fat Diet

Objective:To investigate the effect of orexin-A on food intake and body weight in diet-induced obesity rats.Methods: After acclimation to the housing facilities,male Sprague-Dawley(SD)rats were classified rats as HA or LA on the basis of measurement of ambulatory and stereotypic SPAINT.Some of HA and LA rats were used to establish DIO models.Rats were prepared with unilateral cannulae targeting LH or SN and orexin-A was injected as schedule.Body weight,fat and lean mass,food intake,SPA,indirect Calorimetry(IDC)of rats was measured.Results: There were significant differences in SPA between HA and LA rats but similar in total body weight,fat mass.Higher level of ambulatory SPA was correlated with higher LH orexin responsivity,and orexin regulation of SPA was distributed through multiple brain sites including the LH and SN.Therefore,we proposed that HA rats might have higher LH and SN orexin responsivity compared to LA rats.There were significant differences in LH of HA and LA rats across all doses of orexin among individual doses of OXA against aCSF injection.On the contrary,for SN,there were only significant differences within HA rats at higher OXA.After adjustment for total body mass,HA rats showed significantly higher EE than LA rats(P<0.05)while there were no differences in uncorrected EE between HA and LA rats averaged over IDC recording sessions doses.LA rats had higher DIO sensitivity than HA rats.Conclusions: OrexinA signaling contributes to the observed variations in SPA and DIO sensitivity.