Abstract
PurposeThis 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.MethodsObese 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.ResultsCompared 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).ConclusionThe 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.
Highlights
Active brown adipose tissue (BAT) has been found in adult humans, which is believed to play an important role in metabolic balance in the body [1, 2]
When the BATs are activated, the catecholamine released from sympathetic nerve endings will trigger the b3-adrenergic receptors and lead to high-level expression of uncoupling protein-1 (UCP1) on the inner membrane of mitochondria, which can burn glucose and fatty acids to produce heat through a process known as non-shivering thermogenesis [5]
We examined the feasibility of 18F-FDG microPET imaging of BAT in diabetes mellitus (DM) and obesity disease models, and discovered a significant relationship between BAT function, blood glucose level and body weight change
Summary
Active brown adipose tissue (BAT) has been found in adult humans, which is believed to play an important role in metabolic balance in the body [1, 2]. In some special circumstances, such as in patients with malignant pheochromocytoma [3], the BAT tissues in omental and mesenteric regions can be significantly activated by cold exposure [4]. Some human studies have suggested that obesity might be associated with a decreased volume of BAT [10], and mice studies have shown that absence of BAT activity could aggravate obesity [11, 12]. Blood glucose level has been found to be interrelated with BAT activity, and the ‘‘detectable’’ BAT on 18FFDG PET may serve as a protective factor against DM [13]. The dynamic relationship among BAT metabolism, obesity and DM in vivo still warrants further investigation [16]
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