Metabonomic Study On The Heat Stress And Kisspeptin Intervention

The stress is generated in response to changes in internal and external environment of the body is characterized by systemic reactions to neuroendocrine activation of the immune network.More and more evidence suggests highly activated under stress conditions neuroendocrine immune network will have a strong disorder the well balanced metabolism of living organisms.It is reported that heat stress,commonly occurring in hot weather for human beings,is closely connected with heat shock and tachypnea,cardiac failure,inflammation,and so forth,thereby causing higher mortality,especially among the elderly In livestock industry,heat stress had negative effects on animal growth performance and reproductive ability.It decreased feed intake,increased the occurrence of disease frequency and the consumption of nutrition metabolism of animal,which lead to poor growth of animal and great economic losses.Kisspeptins are encoded by the KISS1 gene in mammals.Numerous studies have shown that Kisspeptin have many important physiological roles in inhibiting of tumor metastasis,regulating reproductive function,and suppressing oxidative stress.However,so far,limited work was focused on heat-stress-induced metabolic alteration and there is also little study involved in Kisspeptin intervention.Heat stress is a systemic and dynamic process which can cause systemic physiological and biochemical alterations in living organisms.For this reason,it is critical that it needs a systemic and dynamic research tool to access and investigate it.Given this above,GC/TOF-MS-based metabonomics research approach was applied to study the significant alterations in metabolite expression induced by heat stress,and Kisspeptin effects on heat stress.Experiment 1:Heat stress can cause systemic physiological and biochemical alterations in living organisms.In this study,serum,hypothalamus,and epididymis samples derived from male SD(Sprague-Dawley)rats being exposed to high environmental temperature(40℃)2 h per day for 7 consecutive days were analyzed using metabonomics strategies based on GC/TOFMS.Differentially expressed metabolites reveal that the energy metabolism,amino acid neurotransmitters,and monoamine neurotransmitters pathways are associated with heat stress,in accordance with changes of the three upstream neuroendocrine system pathways in the SNS(sympathetic adrenergic system),hypothalamic pituitary adrenal axis(HPA),and hypothalamic pituitary testis axis(HPT)axis.Many of these metabolites,especially in the epididymis,were found to be up-regulated,presumably due to a self-preserving action to resist the environmental hot irritation to maintain normal functioning of the male reproductive system.Experiment 2:Attenuating effects of Kisspeptin on oxidant damages in liver of heat stressed rat.The protective effects of Kisspeptin on oxidative stress in liver,which was investigated by using a combination of physicochemical indexes and metabonomics.Metabonomics analyses were performed using gas chromatography/mass spectrometry in conjunction with multivariate and univariate statistical analyses.Our results showed that the activities of liver glutathione peroxidase(GSH-PX),total superoxide dismutase(SOD)and total antioxidant capacity were significantly lower in H group compared with control,and the KH group was significantly higher than that of the H group.Histological observation showed that considerable amount of inflammatory cells and cellular edema were found in liver tissues of Group H rats.In addition,the organelle changes including dilation of rough endoplasmic reticulum,mitochondria swelling and membrane fragmentation were also presented by means of transmission electron microscope.Relief of hyperaemia and edema as well as significantly decrease in organelle changes were observed in KH group.Metabonomic analysis of liver tissue revealed that Kisspeptin mainly attenuated the alteration of fatty acid metabolites,purine metabolites and energy metabolites,such as arachidonate,eicosatetraenoate,lysine,phenylalmine,2-aminobutyrate,allantoin,were significantly higher in heat stress group compared with control group,but had a totally different trend in KH group.These results provide important mechanistic insights into the protective effects of Kisspeptin against heat-stress-induced oxidative stress in the liver.