Regulation Of White Adipose Tissue Browning And Related Lipid Metabolism Of Rats Under Simulated Environment At Altitude Of 5000 M

Background:People living in plains tend to decrease in body fat percentage after enter the plateau.It is known that white adipose tissue(WAT)browning is a process burning fat and releasing calories,resulting in reduced fat mass.However,it is not clear whether hypoxia could induce WATs browning and decrease in body fat percentage through it.Objective:In this study,the hypoxic rat model was constructed.Using the decrease of body fat percentage under altitude hypoxia as a clue,we investigate the phenotypic changes and regulatory mechanisms of WATs browning in different anatomical positions of rats during the adaptation from acute hypoxia to chronic hypoxia,providing theoretical basis for the prevention of altitude diseases and the study of weight loss under hypoxia.Methods:We constructed hypobaric hypoxic rat models by exposing 9-week-old male SD rats to a hypobaric hypoxic chamber for 1,3,14 and 28 days(Group H)under simulated environment at altitude of 5000m.We also established normoxic control groups for each time period(Group C),as well as paired 1-day and 14-day normoxic food-restriction rats that were fed the same amount of food as the hypoxic group ate(Group R).We then observed the growth status of rats and recorded dynamic changes in histologic,cellular and molecular levels of perirenal WATs(PWAT),epididymal WATs(EWAT)and subcutaneous WATs(SWAT)in each group.Results:Hypoxia promoted WAT browning and changed related lipid metabolism of Rats under Simulated Environment at Altitude of 5000 m:1.Hypoxic rats had lower food intake,significantly lower body weight than control rats,and showed lower WATs index.2.In group H14,ASC1,marker of white adipocyte,its mRNA expressions of PWAT and EWAT in rats were lower than that in group C14,and PAT2,marker of beige adipocyte,its mRNA expressions of EWAT were higher than that in both group C14 and R14.In group R14.however.ASC1 mRNA expressions of PWAT and EWAT in rats were higher than both group C14 and H14,and that of SWAT was also significantly higher than group C14.In group H3,both the mRNA and protein levels of WAT browning marker UCP1 of PWAT in rats were increased than group C3.And in group H14,those of EWAT in rats were increased than group C14.3.Changes of lipid metabolism.In plasma of rats,the adiponectin level was significantly lower in H3 than C3,but higher in H14 than C14.The resistin level was significantly higher in H28 than C28.The total cholesterol level in plasma of rats was significantly higher in H1 than C1,but lower in H28 than C28.The free fatty acid level was significantly higher in H14 than C14 and R14,but lower in H28 than C28.In group H3,the mRNA expressions of FASN in both PWAT and EWAT of rats were down-regulated,while those of ATGL were up-regulated.However,in group R14,the mRNA expressions of FASN in both PWAT and EWAT of rats were significantly higher than both C14 and H14.4.Changes of regulators.The mRNA level of HIF-1α in EWAT of rats was significantly higher in H28 than C28.The norepinephrine level in plasma of rats was significantly higher in H3 than C3.In group H3,the mRNA expressions of ADRB3 in both PWAT and EWAT of rats were significantly higher than C3.Conclusion:Under simulated environment at altitude of 5000 m,hypoxia induced WATs browning in rats to promote fat mass loss.Reduced food intake under chronic hypoxia didn’t affect WAT browning in rats.PWAT and EWAT had higher sensitivity to hypoxia than SWAT.