TEMPERATURE-DEPENDENT FEEDING - LACK OF ROLE FOR LEPTIN AND DEFECT INBROWN ADIPOSE TISSUE-ABLATED OBESE MICE

The objective was to characterize the ability of control and transgeni c brown adipose tissue (BAT)-ablated uncoupling protein diphtheria tox in A chain (UCP-DTA) mice to adjust food intake in relation to changes in environmental temperature and to assess the involvement of leptin in this adjustment. We measured serum leptin in mice from a previous s tudy of UCP-DTA mice raised at thermoneutrality (35 degrees C) or at t he usual rearing temperature (24 degrees C) from weaning [Melnyk, A., M.-E. Harper, and J. Himms-Hagen. Am. J. Physiol. 272 (Regulatory Inte grative Comp. Physiol. 41): R1088-R1093, 1997] and extended the study by acclimating control and obese UCP-DTA mice at 18 wk of age to cold (14 degrees C) for up to 14 days. Leptin levels did not change in cont rol mice at 14 degrees C; however, food intake increased threefold wit hin 1 day and remained at this level. Serum leptin level was elevated in UCP-DTA mice at 24 degrees C compared with control mice at 24 degre es C; this elevated level decreased within 1 day at 14 degrees C and w as pot different from the level in control mice by 14 days. Food intak e of UCP-DTA mice that were hyperphagic at 24 degrees C did not change during 7 days at 14 degrees C, then increased slowly. Similar low lep tin levels were present in control mice raised at 24 or 35 degrees C a nd in UCP-DTA mice raised at 35 degrees C. Food intake of control mice raised at 24 degrees C was two times that of control mice raised at 3 5 degrees C. UCP-DTA mice raised at 35 degrees C ate the same low amou nt; as control mice raised at 35 degrees C. UCP-DTA mice at 24 degrees C were hyperphagic relative to control mice at 24 degrees C yet had e levated leptin levels in their serum. Two principal conclusions are dr awn. First, adjustment of food intake over a fourfold range by control mice acclimated to temperatures from 35 down to 14 degrees C is indep endent of changes in serum leptin levels. Second, this adjustment of f ood intake in relation to temperature is defective in the UCP-DTA mous e; the defect leads to hyperphagia at 24 degrees C and a failure to in crease food intake as rapidly as control mice when exposed to 14 degre es C. Because lack. of UCP-1-mediated thermogenesis in BAT of knockout mice is known not to induce hyperphagia, we propose that deficiency o f UCP-1-expressing brown adipocytes in BAT of UCP-DTA mice results in lack of a satiety factor, secreted by these cells in BAT of control mi ce in inverse relationship to sympathetic nervous system activity.