Restoration of fasting‐induced torpor in dopamine beta hydoxylase −/− mice

Many organisms throughout the animal kingdom, including mice, can experience a well‐orchestrated decline in metabolic rate and core body temperature (T b ) in response to, or in anticipation of, a lack of sufficient caloric intake. Previous investigations have shown that the adipocyte‐derived hormone leptin can blunt or even prevent these bouts of torpor. Unlike wildtype counterparts, mice deficient in the enzyme dopamine β hydroxylase (Dbh −/− mice), which are unable to synthesize epinephrine and norepinephrine, do not reduce circulating leptin upon fasting nor do they enter torpor. To test the hypothesis that the onset of torpor bouts in mice during a fast requires sympathetically‐mediated reduction in circulating leptin, mice deficient in both leptin and the enzyme dbh (DBL KO) were generated. Both ob/ob mice, which are deficient in leptin, and the DBL KO mice were obese at 6 months of age (approximately 60 grams) and ate 60% more food (5 grams per day vs. 3 grams per day for counterparts). This suggests that Epi and NE play little role in the mechanism of leptin‐deficient obesity. Upon fasting, wildtype and ob/ob mice entered torpor as assessed by telemetric core Tb acquisition (WT min T b = 23.9 ± 0.4: ob/ob min T b = 23.8 ± 0.4 C), whereas the length of torpor was significantly longer in ob/ob mice vs. WT (633 ± 53 vs. 359 ± 35 minutes, respectively). Both ob/ob and WT mice entered torpor about 7 hours after initiation of the fast. As we have seen previously Dbh −/− mice did not enter torpor with fasting. The DBL KO mice entered torpor upon fasting (min. T b = 24.3 ± 0.4 C), did so within the first 30 minutes of fasting, and remained in the torpor bout twice as long as ob/ob mice (1155 ± 42 minutes). These data are consistent with our hypothesis that sympathetic activation of white fat is required for the onset of torpor, and that catecholamines are important in recovery from a bout of torpor.