ARCHIVES OF BIOCHEMISTRY AlriD BIOPHYSICS 114, 494-%1 (1966) Cold-Acclimatization and intermediary Metabolism of Carbohydrates’ GEORGE R. MORRISON,2 FRANCES E. BROCK, DEJANO T. SOBRAL, AND ROBERT E. SHANK Department of Preventive Medicine, Washington University School of Medicine, St. Louis, Missouri Received December 13, 1965 The activities of 14 enzymes participating in the intermediary metabolism of carbohydrates have been measured in the livers of rats to study the effects of chronic cold exposure. Based upon significant alterations in the activities of rate-limit,ing enzymes, it is concluded that an improved capacity for gluconeogenesis is the major change in hepatic carbohydrate metabolism associated with cold-acclimatization. No significant alterations in the activities of enzymes which are rate-limiting for glycolysis, glycogenesis, or glycogenolysis were found in the livers of rats exposed to 4” for 28 days. The ability of mammals to survive in a cold environment and to resist cold injury depends upon their capacity to increase body heat production. When an animal becomes cold-acclimatized, increased heat produc- tion is accomplished without shivering (non- shivering thermogenesis) (1) ; his basal metabolic rate in the cold and at room temperature is increased (2) but there is minimal electrical activity of skeletal muscle in the cold (3). An increased tot,al body utilization of carbohydrates (4, 5), fats (6), and proteins (7) contributes to the increased metabolism. The liver of the cold-acclimatized animal participates in the increased body heat production. Not only is the liver enlarged (8) but there is an increase in the rate of oxygen consumption per unit weight of liver (9-12). The thermal demands of a cold en- 1 This investigation was supported by the United States Army Medical Research and De- velopment Command, Office of the Surgeon Gen- eral, under Contract No. DA-4%007-MD-1024, by grant AM-06309, National Institutes of Health, U.S.P.H.S., and by grant 5 TI AM 5341-05(n), National Institutes of Health, U.S.P.H.S. *John and Mary R. Markle Scholar in Medical Science. vironment are such that the cold-acclima- tized animal gains weight more slowly than its warm-acclimatized counterpart (5, 13,14) even though the animal consumes greater amounts of food (14-16). Nevertheless, the increased hepatic metabolism of the cold- acclimatized animal permits maintenance of a normal fasting blood sugar (17) and the accumulation of glycogen in the liver with feeding (5, 8). Such findings have stimulated investigations into the alterations in inter- mediary carbohydrate metabolism of the liver that are associated with chronic cold exposure. Because the reports of these investigations do not afford total explanat.ion, as pointed out in the discussion, of the alterations in intermediate carbohydrate metabolism which are associated with cold-acclimatization, the experiments described here were in- itiated. The act,ivities of 14 enzymes, eight of which have not been studied previously in chronically cold exposed animals, were measured in homogenates of rats exposed to ambient temperatures of 4” and 24” for 28 days to seek evidence of hepatic alterations in glycogenesis, glycogenolysis, glycolysis, gluconeogenesis, and the pentose pathway that are associated with cold-acclimatiza- 494