Objectives: The peripheral insulin resistance associated with burn injury has been demonstrated in muscle, liver and white adipose tissue (WAT). However, little is known about the potential role of brown adipose tissue (BAT) in burn-induced insulin resistance. The aim of the present study, therefore, was to determine the insulin signaling, stress kinases activities and adipocytokines expressions in BAT following burn injury to mice.
Methods :The methods used in this study involved mice, Western Blot and real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), as well as measurement of glucose uptake using the positron emitting tracer (PET) 2-fluoro-2-deoxy-D-Glucose (FDG).
Results: The results show that content of IRS-1 protein is slightly increased, and no changes of phosphorylation of IRS-1 serine 307, accompany with no increasing of stress kinases activities. The mRNA expression levels of IRS-1, IRS-2 and GLUT4 are decreased by 50%, 65% and 15%, respectively. Burn injury activates the BAT and increases FDG uptake into BAT.
A dramatically increased expression of UCP1 gene (approximately 18-fold) was observed. Burn injury resulted in significant increases in the level of IL-6 (5-fold) and TNF-α mRNA (1.6 fold). In contrast, burn injury also resulted in a 90% and 60% decrease in leptin and adiponectin respectively.
Conclusions: All these results collectively indicate that 1) down-regulated mRNA expression of key proteins in the insulin signaling cascades may play important roles in the burn-induced insulin resistance in BAT. 2) Burn trauma stimulated glucose utilization in BAT may be due, at least in part, to the activation of UCP1. 3) The mRNA levels of adipocytokines proteins (TNF-α, IL-6, leptin, adiponectin) involved in the regulation of lipid and glucose metabolism and energy expenditure were profoundly modified by burn injury. The data suggest a novel role of brown adipose tissue in the regulation of glucose homeostasis following burn injury.
Key words: Burn; brown adipose tissue; insulin resistance; adipocytokines.
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