Bariatric surgery remains the only effective treatment for morbid obesity. Vertical sleeve gastrectomy(VSG) is the most widely performed of the bariatric surgeries, largely because it confers not only significant weight loss but improved glucose regulation. We have recently demonstrated that brown adipose tissue(BAT) temperature and UCP1 protein expression in BAT are elevated following VSG and contribute substantially to weight loss. However, the importance of BAT in the mediation of improved glucose regulation following VSG is unclear.
Diet-induced obese male Sprague-Dawley rats underwent VSG (or sham) surgery and were also implanted with a telemeter to measure local changes in brown fat temperature, indicative of brown fat activity. Eight weeks following VSG surgery, oral and intraperitoneal glucose tolerance tests(GTTs) were performed to assess glycemic function. To localize glucose uptake in specific tissues, an oral GTT (1.5g/kg) was combined with an intraperitoneal injection of 40µCi of deoxy-D-glucose,2-[1-14C] (2DG-14C), administered intraperitoneally. Blood was collected immediately before the injection of 2DG-14C and glucose gavage (time 0) as well as 2, 5, 10, 20, 30 minutes later. Immediately after the final blood collection (30min), rats were killed and tissues were rapidly dissected for assessment of 2DG-14C uptake.
Following VSG, there is a rapid reduction in body weight that is maintained for 8 weeks post- surgery. VSG is associated with increased BAT temperature 3 days post-surgery that is also maintained throughout the 8-week treatment period. There is improved glucose regulation coincident with the elevation in BAT activity following VSG as demonstrated by improved glucose clearance during the GTT and elevated glucose stimulated insulin secretion. Importantly, the pivotal role of brown fat is demonstrated by significantly elevated (4-fold) glucose uptake into BAT followed VSG compared to sham operated animals.
Collectively, these data support a role for BAT in mediating the improvement in glucose regulation following VSG surgery.