Activating Brown Adipose Tissue for Weight Loss and Lowering of Blood Glucose Levels: A MicroPET Study Using Obese and Diabetic Model Mice

PLoS One

Fengying Gong¹  Huijuan Zhu¹  Naishi Li¹  Zhaohui Zhu²  Chenxi Wu²  Yi Sun²  Wuying Cheng²  Fang Li²  Yonghong Dang² 

[1] Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

关键词: Obesity;    Brown adipose tissue;    Mouse models;    Diabetes mellitus;    Blood sugar;    Glucose metabolism;    Positron emission tomography;    Thyroid hormones;   

DOI  :  10.1371/journal.pone.0113742

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Purpose This study aims at using 18F-FDG microPET to monitor the brown adipose tissue (BAT) glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models.Methods Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist) or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels.Results Compared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and <0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = −0.71, P = 0.003) and DM mice (r = −0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45).Conclusion The inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM.

【 授权许可】

CC BY