Brown adipose tissue metabolism may be related to sympathetic activation: a preliminary study with m

来源 :The 1st Sino-American Conference on Nuclear Medicine(首届中美核医学 | 被引量 : 0次 | 上传用户:m116730647
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  Objective: This study aims at using 18F-FDG microPET to evaluate several interventions related to Sympathetic Nerve System (SNS) in stimulation and inhibition of brown adipose tissue (BAT),and to study the role of BRL37344, an adrenergic β3 receptor agonist, in activation of BAT metabolism in normal mice, type 2 diabetes model mice, and obese model mice receiving weight-loss treatment (weight-loss mice).Method: Six to seven week-old ICR mice were enrolled.To study the physical interventions, normal mice were exposed to cold (6-7℃, n=6), warm (35℃, n=6), cold and then warm (n=6), or constant temperature of 21±3℃ (n=12) for 1 h.In pharmacological interventions, normal mice received either intraperitoneal injection of norepinephrine (NE, 0.4mg/kg, n=5), epinephrine (0.02mg/kg, n=5), isoprenaline (0.016mg/kg, n=6), or intragastric administration of propranolol (13.2mg/kg, n=3).To study the role of BRL37344, 24 mice were randomly divided into three groups: the normal control group (group 1, n=12), the type 2 diabetes group (group 2, n=6), and the weight-loss group (group 3, n=6).Group 2 and 3 were bred with high fat diet for eight weeks.We use Streptozocin (STZ, 100mg/kg) to build type 2 diabetes model in group 2, and Sibutramine (8mg/kg) gavage for two weeks daily to build weight-loss mouse model in group 3.All the three groups received peritoneal injection of either BRL37344 (2mg/kg) or saline half to half for each group.MicroPET scans were performed lh after intraperitoneal injection of 3.7 MBq 18F-FDG,and the FDG uptake ratio (R) between interscapular BAT and liver (or brain) was calculated in each mouse for semi-quantitative analysis.Result: Stimulation of SNS by cold or NE significantly increased BAT uptake (R: 10.22±4.13 vs 4.08±1.32, P=1.96×10-4, and 10.55±5.85 vs 4.08±1.32, P=0.002, respectively), and much higher BAT uptake was observed under both interventions (R: 15.64±5.58 vs 4.08±1.32, P=2.19×10-6).Epinephrine and isoprenaline intervention didnt show significant increase of BAT uptake of FDG (P=0.459 and 0.293, respectively).Inhibiting SNS by warming up or propranolol administration could significantly reduce BAT uptake in mice (R: 2.48±0.88 vs 4.08±1.32, P=0.017, 1.30±0.16 vs 3.09±0.90, P=0.027, respectively).BAT metabolism could be significantly stimulated by BRL37344 treatment in normal mice and weight-loss mice (R: 30.0±23.3 VS 8.6±2.7, P<0.05,16.8±5.07 vs 5.4±3.92, P<0.05, respectively), but could not significantly activate the BAT in diabetes mice (R: 5.1±3.98 vs 6.8±1.76, P>0.05).Under the stimulation of BRL37344, BAT metabolism was the highest in normal mice and the lowest in type 2 diabetes mouse (R: 30.0±23.3 and 5.4±3.92, respectively, P<0.05).Conclusion: BAT metabolism has a positive correlation with SNS activation; stimulation or inhibition of SNS by physical or pharmacological methods may increase or decrease BAT metabolism correspondingly.Type 2 diabetes is coincident with BATs dysfunction or desensitization to stimulating factors such as BRL37344.Weight-loss treatment, using Sibutramine for example, is related to the increase of BATs sensitivity to adrenergic β3 receptor agonist.
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