Manipulation of Brown Adipose Tissue Alters Energy Expenditure in Mice

When energy intake is greater than energy expenditure, extra calories are primarily stored in white fat and leads to obesity. In contrast, brown adipose tissue (BAT) is an energy-burning type of fat that counteracts obesity. We hypothesize that increase in quantity of active BAT improves energy homeostasis.  First we developed a BAT transplantation surgery. Transplanted BAT had normal appearance with blood vessels and nerve fibers. Additionally transplanted and endogenous BAT had similar expression of thermogenesis-related genes UCP1 and PGC-1α, suggesting sympathetically regulated thermogenic function of transplanted BAT. Second, we tested how BAT transplanted mice respond to sympathetically activated conditions. Sham-operated and recipient mice responded similarly to cold exposure with similar BAT-specific temperature. Furthermore, sham-operated and recipient mice increased their heat productions to the same level during norepinephrine challenge test. However, recipient mice had greater oxygen consumption, suggesting that energy expenditure is elevated to a greater extent following BAT transplantation. Third, we asked whether BAT transplantation regulates energy balance during obesity development. Half of sham-operated mice and recipients were switched to a high-fat diet (HFD-sham, HFD-BAT), and the rest were maintained on standard chow.  Both HFD groups comparably consumed more calories than the chow groups. However HFD-BAT mice gained less adiposity than HFD-sham mice with increased oxygen consumption and lowered respiratory quotient, indicating greater energy expenditure and reduced fat oxidation as fuel source in HFD-BAT mice. In summary, mice with brown fat transplantation respond normally to sympathetically challenged conditions but exhibited a partial resistance to obesity due to increased energy expenditure.