[The role of ketone bodies in nonshivering thermogenesis in cold-adapted rats (author's transl)].

In spite of the ill fame of useless products of metabolism that only accumulate in the blood under abnormal conditions, ketone bodies (KB) have now regained the fame as an important fuel of respiration for the brain and muscles in prolonged starvation in humans and other animals. In cold-adapted animals, ketosis has been well documented, but little is known about the physiological role of KB in cold adaptation. In this study, role of KB in nonshivering thermogenesis was investigated in warm- and cold-adapted rats with or without norepinephrine (NE) loads, a decisive lipid metabolizing hormone in cold adaptation. First, levels of blood KB and plasma free fatty acid (FFA) and FFA turnover rate were examined along with rectal temperature under continuous infusions of various doses of NE. Good dose-response relationship of rectal temperature was obtained with increasing doses of NE in cold-adapted rats, but not in warm-adapted ones. The levels of blood KB and plasma FFA in cold-adapted rats remained almost unaltered during the observation period of 30 minutes. Infusion of NE, however, greatly enhanced FFA turnover rate in cold-adapted rats as compared with controls. Next, fractional turnover rate and half-life of beta-OH-butyrate were obtained from decay curves of endogenous beta-OH-butyrate, using functionally eviscerated rats in which no KB were produced. Calculated turnover rate of KB was also found significantly increased in cold-adapted rats. Finally, the effect of NE on the production of KB was examined using the liver in situ perfusion technique of Mortimore with minor modifications. Viability of the liver preparation was guaranteed by sufficiently high rates of bile production as well as oxygen consumption. The production rate of KB in the preparation under palmitate loads of physiological medium concentration was significantly higher in cold-adapted rats than in warm-adapted controls. However, no significant effect of NE loaded simultaneously was observed in either group. Quantitative analysis shows that the turnover rate of KB in vivo essentially equals the production rate in the perfused liver when no exogenous NE is added. In contrast NE infusion the turnover rate in vivo was almost doubled that of the perfused liver. All these results indicate KB are used as an important energy source with the significancy of FFA in nonshivering thermogenesis. Moreover, it may be surmised that production of KB in vivo, particulary in the cold-adapted state, is effected by other unknown factors than NE.