Cold-induced Changes in Uncoupling Protein and GDP Binding Sites in Brown Fat of Ob/ob Mice

The acute and chronic effects of cold exposure on the thermogenic activity and capacity of brown fat of obese (ob/ob) and lean mice have been examined. After 1 h at 13 degrees C, mitochondrial GDP binding increased in warm-acclimated (28 degrees C for 3 wk) lean mice, and increases in mitochondrial mass and the specific mitochondrial concentration of uncoupling protein were evident at 24 h. Long-term cold exposure led to further progressive increases in the specific mitochondrial concentration and total tissue content of uncoupling protein. The acute increase in GDP binding was due to an unmasking of binding sites on the protein and was accompanied by a parallel increase in the acetate-induced swelling of the mitochondria. In contrast to lean animals, ob/ob mice did not exhibit an increase in GDP binding or unmasking of binding sites during the first 24 h of cold exposure; unmasking was, however, evident by 3 days. A delay in the stimulation by cold of both the specific mitochondrial concentration of uncoupling protein (not increased until 3 days) and the mitochondrial content of brown fat (not increased until 8 days) occurred in the obese mice. Acute warm exposure (28 degrees C) of cold-acclimated (13 degrees C for 3 wk) mice led to a reduction in GDP binding in both lean and obese animals because of a rapid masking of binding sites. Mitochondrial content and the specific mitochondrial concentration of uncoupling protein fell progressively in both groups of mice with continued warm exposure.(ABSTRACT TRUNCATED AT 250 WORDS)