Activating brown adipose tissue for weight loss and lowering of blood glucose levels: a microPET study using obese and diabetic model mice

PLoS One. 2014 Dec 2;9(12):e113742. doi: 10.1371/journal.pone.0113742. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Blood Glucose
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy
  • Diet, High-Fat
  • Fluorodeoxyglucose F18 / administration & dosage
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Insulin / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, Obese
  • Obesity / metabolism*
  • Obesity / pathology
  • Obesity / therapy
  • Positron-Emission Tomography
  • Weight Loss*

Substances

  • Blood Glucose
  • Insulin
  • Fluorodeoxyglucose F18

Grant support

This work is supported by National Natural Science Foundation of China (NSFC) (No. 81101074, No. 81371588); Graduate Student Innovation Foundation of PUMCH (No. 2011-1002-25); 2012 Young and Middle-aged Researcher Science Fund of PUMCH, funding from Key Laboratory of Endocrinology of Health and Family Planning Committee, and an UCSF-PUMCH RAP funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.