| BackgroundMetabolism-related diseases such as obesity and its complications has reduced peoples quality of life,but there are few effective treatment options and new targets are needed.Brown adipose tissue(BAT),due to its mitochondria containing specific uncoupling protein 1(UCP1),is able to utilize fatty acids for non-shivering thermogenesis during the uncoupling of the oxidative respiratory chain.The release of heat reduces fat accumulation and contributes to energy balance,and the effective activation of BAT can achieve the purpose of weight loss,which is expected to be a therapeutic target in the fight against obesity and its complications.In vivo imaging technology is crucial for understanding the physiology and function of BAT,and accurate identification of BAT and non-invasive assessment for its active status is the key to weight loss targeting BAT.Purpose1.To investigate the feasibility of MR quantitative susceptibility mapping(QSM)in identifying and evaluating brown adipose tissue through acute cold stimulated experiment in the interscapular region of normal rat,and histological verification was performed.2.To investigate the change of fat fraction(FF)value in brown adipose tissue after intermittent cold stimulation in obese rats induced by high fat diet.Materials and methods1.Fifteen male Sprague-Dawley(SD)rats were randomly divided into control group(n=5),cold stimulated group for 12h(n=5)and cold stimulated group for 24h(n=5).The rats of cold stimulation group were exposed at 4℃ for 12h and 24h,respectively,while the other animals were fed at room temperature.MRI scans were performed immediately after cold stimulation.A 3D multi-echo gradient(GRE)sequences were scanned in the interscapular region for BAT and WAT,then FF,QSM and R2*were calculated.The H&E-stained slides of interscapular brown adipose tissue and white adipose tissue were analyzed.The expression of protein associated with energy metabolism(UCP1)in the brown adipose tissue was assayed by Western blotting.2.SD male rats(n=30)were randomly divided into three groups:control group(n=10),high fat diet group(HFD,n=10)and high fat diet with cold stimulation group(HFD+4℃,n=10),MRI scan and histological analysis were performed on all animals after 4 and 8 weeks,respectively.Experimental animals were imaged on 3T using chemical shift water-fat separation magnetic resonance imaging(mDixon-Quant),and FF value was calculated.Samples were collected immediately after the scan for H&E staining analysis.Results1.The QSM values of WAT after cold stimulation for 12h(0.19±0.12)and 24h(0.21±0.13)were lower than those of the control group(0.55±0.09)(P<0.05),while the measured values of FF and R2*had no significance(P>0.05).The FF(12.27±4.06,13.98±2.29),QSM(-0.04±0.05,0.06±0.05)and R2*(100.83±13.73,120.83±23.94)values of BAT after cold stimulation for 12h and 24h were significantly lower than the values of FF(46.40±5.28),QSM(0.32±0.06)and R2*(175.27±14.82)in the control group(P<0.05).In addition,BAT had higher UCP1 expression,FF and QSM values were negatively correlated with UCP1 expression levels in BAT(r=-0.7930,-0.6385 and-0.5786,P<0.05).2.After 4 or 8 weeks of high fat diet,the weight of rats in the HFD+4℃ group was increased compared with the control group.The weight of rats in the HFD+4℃group was decreased compared with the control group and the HFD group at 4weeks and 8 weeks.Significant differences were observed in BAT FF between control group,high fat diet group and high fat diet with cold stimulation group(P<0.05)at 4 and 8 weeks,and the FF value of BAT in the HFD and HFD+4℃ groups were higher than that in the control group.The FF values of BAT in the three groups at 4 weeks(38.51±13.21,65.90±7.98,62.12±3.23)were all lower than that at 8 weeks(60.56±8.02,70.96±5.21,71.83±1.69),and there was statistical difference in the control group and the HFD+4℃ group(P<0.05).H&E analysis showed that compared with the control group,the vacuolated lipid droplets of brown adipose tissue increased in rat induced by high fat diet for 4 or 8 weeks,while the little change was observed in the HFD+4℃group compared with the HFD group.Compared with 4 weeks,the number of lipid droplets in BAT all increased in three groups at 8weeks.Conclusion1.FF,QSM,and R2*maps generated from 3D multi-echo GRE sequences offer the possibility of detecting BAT and evaluating its activity quantitatively,and the results are highly correlated with histological analysis.QSM is expected to be used as a potential imaging marker to observe BAT and evaluate the activated status of BAT.2.The metabolic activity of BAT in obese rats induced by high fat diet was weakened and the FF value of BAT increased.Intermittent cold stimulation alone could counteract weight gain in rats fed high fat diet to a certain extent,but the expected activated BAT was not obvious,the corresponding change of FF value of BAT was also not obvious.The changes of FF value in BAT were consistent with the changes of histology,FF may be a potential non-invasive quantitative indicator of changes in BAT metabolism. |
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