Brown adipose tissue (BAT) can normalize hyperglycemia and hypertriglyceridemia in mice

Aims: In adults, less than 1% of total adipose tissue is brown adipose tissue (BAT). It had been suggested, that BAT is only important for non shivering thermogenesis in newborn and rodents. A major role in the metabolism of adult humans was not supposed. However, based on recent studies using PET-CT, this had to be revised: After cold exposure, BAT was found in most of subjects investigated. A significant glucose uptake of several grams per day into BAT was measured. The aim of the present study was to further investigate the metabolic function of BAT.

Methods: Mice with diet induced obesity (DIO) and mice with homozygote apoproteinA5 (apoA5) deficiency were investigated for responses in glucose and lipid metabolism during and after cold exposure (4°C, 4 to 24h). Results were compared to normal, not temperature challenged littermate controls.

Results: As previously shown, DIO mice have an impaired glucose tolerance. Fasting glucose stayed stable during cold exposure. On ambient temperature, during oral glucose tolerance test, plasma glucose raises up to 420mg/dl. However, after cold exposure, the glucose peak was significantly reduced reaching a maximum of 310mg/dl. Lean control mice without impaired glucose tolerance did not show any cold induced changes in glucose metabolism.

ApoA5-deficient animals suffer a severe, genetically caused hypertriglyceridemia with triglycerides above 2300mg/dl. During cold exposure, in these animals plasma triglyceride levels fell after 4h to 700mg/dl, reaching completely normal values after 24h. Initially lipidemic plasma cleared completely during cold exposure. Metabolic turnover and organ uptake studies using lipoproteins (VLDL and chylomicrons radioactively labelled at their triglyceride and apoprotein residues) showed that BAT was able to multiply its lipid uptake after cold exposure reaching levels more than 10fold, far beyond the lipid uptake into the liver, which stayed constant. At the same time, the normal postprandial triglyceride peak was completely abolished.

Conclusion: These data demonstrate that BAT can multiply its metabolic activity after cold activation. By doing this, BAT is able to completely normalize severe disturbances in glucose and lipid metabolism.