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Brown adipose tissue and non-shivering thermogenesis
Abstracts--Strategies , . cold Symposum
97
The Wenner--Gren l o s t l t u t e , U n i v e r s i t y of Stockholm, N o r r tullsgatan 16, S-I13 45 Stockholm, Sweden. At low t e m p e r a t u r e a c e t a t e has been d e ~ n s t r a t e d to be a major e n d - p r o d u c t o f f a t t y a c i d o x i d a t i o n i n brown a d i p o s e t i s s u e m l t o c h o n d r i a from h a m s t e r s . In i s o l a t e d brown a d i p o VOLUNTARY C O NT R IB UTI ONS ON "THERMOGENESIS c y t e s n o r e p i n e p h r i n e (NE) i s t h e n a t u r a l th e r mo g e n ic e f f e c t o r which s t i m u l a t e s l i p o l y s i s and i n c r e a s e oxygen consumption. F r e e f a t t y a c i d s can r e p l a c e NE a s a s t i m u l a t o r o f AND TEMPERATURE REGULATION" oxygen consumption. The aim o f our i n v e s t i g a t i o n i s to study to what e x t e n t t h e f r e e f a t t y a c i d - i n d u c e d r e s p i r a t i o n i n C h a i r m a n : W i l l i a m R. D a w s o n ( U n i v e r s i t y of M i c h i g a n ) i s o l a t e d hamster brown s d i p o c y t e s r e p r e s e n t e d p r o d u c t i o n o f c i t r i c a c i d c y c l e i n t e r m e d i a t e s and a c e t a t e . As t h e hamster, a h i b e r n a t o r , can v a r y i t s body t e m p e r a t u r e between about CENTRAL AND PERIPHERAL INTERACTIONS IN THE CONTROL OF TRER38"C and 5"C, the temperature dependence of these pathways was investigated. Isolated brown adipocytes were incubated MOGENESIS. E. Z e i a b e r g e r , Zentrum fur P h y s i o l o g i e , J u s t u s i n K r e b s - g l n g e r - p h o s p h a t e - b u f f e r (KRPB) i n an oxygen e l e c L l e b l g - U n i v e r s l t g t Gle~sen, Aulweg 129, D-63 Gtessen. t r o d e chamber and oxygen consumption was measured a s a f u n c An e s s e n t i a l f e a t u r e o f a c u t e c o l d exposure i s t h e a c t i t i o n of added NE or palmitic acid. Halo,ate was used to test v a t i o n of the p e r i p h e r a l s y m p a t h e t i c system. The n o r a d r e n a to what extent the rate of oxygen consumption was dependent l i n e (NA) l i b e r a t e d from t h i s system r e d u c e s h e a t l o s s and promotes heat p r o d u c t i o n mechanisms. NA i s a l s o known to I n - on the citric acid cycle. At 370C in KRPB bubbled with 5Z f l u e n c e the hypothalamic thermoregulatory centers. The mean CO 2 in air the maximal oxygen consumption upon NE stimulabody temperature at which guinea plgs start to shiver (~b-Sh) tion was 490 nmol O2/mln x 106 cells, of which about 75% represents th e citric acid cycle, and 23%, which cannot be inhas been found to be increased after an intrahypothalamic hibited by ~alonate, represents fatty acid oxidation s t o p p (i.h.) mlcroinJection o f NA and d e c r e a s e d a f t e r i . h . a p p l i in g a t th e a c e t y l - C o A l e v e l . At 30°C 50% r e p r e s e n t s th e c i c a t i o n of an o-adrenerglc b l o c k e r (Zeisberger & BrUck: PflUt r i c acid cycle and 50% th e acetyl-level, while at 2O°C as gets Arch. 362, 113, 1976). Electrical stimulation of the much as 77% of the maximal NE-inducible oxygen consumption lower brain stem at sites presumed to be parts of the asr a t e r e p r e s e n t s end p r o d u c t s a t t h e a c e t y l - l e v e l . Acetate cending catecholamlnerglc pathways (ACP) had the same effect l e v e l s in l i v i n g h a m s t e r s were measured by a n a l y s i n g blood as i . h . NA m i c r o i n J e c t i o n ( S z e l ~ n y l e t a Z . : P f l U g e r s Arch. samples w i t h an enzymatic a s s a y i n a s p e c t r o p h o t o m e t e r . The 364, 123, 1976). The s e n s i t i v i t y to i.h. NA microlnJection acetate concentration in blood from warm-adapted, cold-adapwas h i g h e r in c o l d a d a p t e d (CA) and i n newborn (NB) t h a n in warm a d a p t e d (WA) g u i n e a p i g s . The s e n s i t i v i t y to i . h . phen- ted and h i b e r n a t i n g h a m s t e r s were i n th e mmolar r a n g e , w i t h These d a t a t o l a m i n e i n j e c t i o n s was r e c i p r o c a l l y r e l a t e d . T h i s i n d i c a t e s the highest values found in hibernating animals t o g e t h e r with o ld literature references reporting gQ-values t h a t t h e a c t i v i t y in t h e ACP Is h i g h e r in WA than i n CA or i n NB a n i m a l s . By c o n t r a s t t h e p e r i p h e r a l r e l e a s e of NA i s lower than 0.7 measured during hibernation could indicate i n c r e a s e d i n CA a n i m a l s exposed t o c o l d and i s g r e a t e r in NB that acetate is an important "end" product in brown adipose tissue during hibernation and/or arousal from hlbernat Ion. a n i m a l s than in WA a n i m a l s even a t n e u t r a l t e m p e r a t u r e . In o r d e r t o answer t h e q u e s t i o n whether t h e NA r e l e a s e d p e r i p h e r a l l y i n f l u e n c e s t h e n e u r a l a c t i v i t y i n t h e ACP, the p e r i p h e r a l NA level in NA guinea pigs was increased by i.m. NA ULTKASTRUCTURAL DEMONSTRATIONOF A UNILOCULAR TO MULTIi n f u s i o n ( 1 . 3 mE/ks • h) l a s t i n g 2 h r s and t h e e f f e c t on LOCULAR TRANSFORMATIONOF ADIPOCYTES IN DEVELOPING HAMSTER T b - S h w a s studied. The Tb-Sh was lowered by I"C as early as INTERSCAPULAR ADIPOSE TISSUE. POSSIBLE ROLE OF THE 15 minutes after the beginning of the infusion. After the SYMPATHETIC INNERVATION. Myriam N~chad. The Wenner-Gren infusion the Tb-Sh remained low for at least 3 hours. By contrast i.m. infusion of adrenaline increased the~b-Sh. It Institute, University of Stockholm, Norrtullsgatan 16, S-I13 45 Stockholm, Sweden. is concluded that the high peripheral NA level supresses the During the development of Interscapular adipose tissue a c t i v i t y in the ACP by some negative feedback mechanism. in the hamster, the adipocytes are first not multi- but Thlscould be the basic mechanism of the cold-adaptive shift unilocular. The development of the multilocularity does of Tb-Sh. not start before shout 4 days pos~ p~tt#~and is complete by 15 days post pa~-~um. We have investigated this process by e l e c t r o n m i c r o s c o p y , n o r e p l n e p h r i n e d e t e r m i n a t i o n s and light microscopic autoradlography. We o b s e r v e d two diffBROWN ADIPOSE TISSUE AND NON-SHIVERING THERMOGENESIS Barbara Cannon, Jan Nedergaard, Ulf Sundin and Olv erentiatlon pathways occurring simultaneously: (I) formL t n d b e r g . The Wenner-Gren I n s t i t u t e , U n i v e r s i t y o f ation o f m u l t i l o c u l a r a d i p o c y t e p r e c u r s o r c e l l s from Stockholm, N o r r t u l l s g a t a n 16, $-113 45 Stockholm, e n d o t h e l i a l c e l l s as p r e v i o u s l y d e s c r i b e d ; (2) d i r e c t Sweden. transformation of uni- into m u l t i l o c u l a r adlpocytes By mlcrocalorimetric measurements we have recently showing th e same c h a r a c t e r i s t i c development of th e chondd e m o n s t r a t e d chat t h e h e a t i n g c a p a c i t y of brown f a t in rlome a s in pathway ( I ) and f o r m a t i o n of s m a l l f a t d r o p l e t s h a m s t e r s i s low when c a l c u l a t e d on t h e b a s i s o f t h e whole i n th e p e r i p h e r a l c y t o p l a s m . By 12-15 d a y s , the u l t r a a n i m a l . N o n e t h e l e s s , t h e r e i s an e x t r e m e l y h i g h oxygen c o n structure of these cells has become indlstlnguishable from sumption in the t i s s u e and t h e r e f o r e c o n s i d e r a b l e l o c a l those formed via (1). Such direct transformation of white heat evolution. The high rate of oxygen utilisation rei n t o brown f a t h a s been r e p o r t e d i n a d u l t human p e r i r e n a l quires either a high ATP synthesizing capacity Of the mltofat i n association with e.g. s e v e r e chronic hypoxemia chondrla together with a high rate of ATP hydrolysis oP and pheochromacytoma. In the developing hamster brown fat, a loosening of coupling between oxygen consumption and ATP i t o c c u r s p a r a l l e l w i t h a marked i n c r e a s e i n t i s s u e n o r synthesis. We have demonstrated in isolated mitochondrla epinephrine concentration. The d e n s i t y o f s y m p a t h e t i c that an ATP syntheslsin K system which could parallel the n e r v e f i b r e s i s b e i n g i n v e s t i g a t e d by l i g h t m i c r o s c o p i c r e s p i r a t o r y a c t i v i t y found d u r i n g t h e r m o g e n e s i s i s not p r e sutoradiography. s e n t in brown f a t m i t o c h o n d r i a from h a m s t e r . Instead, a l o o s e n i n g of c o u p l i n g i s r e q u i r e d which i n some manner seems to involve c y t o p l a s m i c p u r l n e n u c l e o t i d e s ( e g . GDP). SUPRACRIASMATIC DINUCLEAR LESION ALTERS CIRCADIAN TEMPERATURE When GDP i s bound t o a s p e c i f i c membrane p r o t e i n o f i s o l a R H Y T ~ ' S AMPLITUDE AND TIMING IN LIGHT-DARK SYNCHRONIZED RATS. t e d , uncoupled m i t o c h o n d r i a , they become c a p a b l e o f e n e r g y P o w e l l , E . N . , J . N . P a s l e y , B. Brockway, L.E. S c h e v i n g , W. Luconservation. In t h e thermogenic c e l l acyl-CoA w i l l be p r o b a n o v ic and F. H a l b e r g . U n i v e r s i t i e s o f M i n n e s o t a , M i n n e a p o l i s , duced and we have shown t h a t low c o n c e n t r a t i o n s o f p a l m i M i n n . , 55455, and A r k a n s a s , L i t t l e Rock, 72201, USA toyl-CoA c a n remove GDP from its m i t o c h o n d r i a l b i n d i n g s i t e . I n t r a p e r l t o n e a l t e m p e r a t u r e was t e l e m e t e r e d (Space L i f e T h i s a c t i o n would f a c i l i t a t e a loosening of coupling. The S c i e n c e 2 : 4 3 7 , 1971) a t l O ' - I n t e r v a l s f o r 9 days from young a p p a r e n t Km f o r o x i d a t i o n of acyl-CoA i s h i g h so i t i s f e a a d u l t male i n b r e d F i s h e r r a t s k e p t a t 24 ± l ' C e n v i r o n m e n t a l s i b l e t o t h i n k t h a t e l e v a t e d acyl-CoA c o n c e n t r a t i o n s can t e m p e r a t u r e w i t h food and w a t e r f r e e l y a v a i l a b l e , s i n g l y i n be found a t l e a s t l o c a l l y . When e n t r y i n t o the c i t r i c a c i d c a g e s measuring 6 ' ~ x 5"H x 10'% i n l i g h t ( a p p r o x l m a t e l y 25 c y c l e i s l i m i t i n g ( e g . due to l a c k of c o n d e n s i n g p a r t n e r ) l u x ) and d a r k n e s s a l t e r n a t i n g e v e r y 1 2 - h (LD 1 2 : 1 2 ) . The r a t s acyl-CoA combustion w i l l o n l y p r e c e e d t h r o u g h ~ - o x i d a t i o n had been o p e r a t e d upon under a n e s t h e s i a t w i c e , f i r s t f o r to t h e a c e t y l l e v e l . High r a t e s o f o x i d a t i o n demand t h a t p l a c i n g s t e r e o t a x l c a l l y an e l e c t r o l y t i c l e s i o n o f t h e s u p r a t h e l e v e l of c i t r i c a c i d c y c l e i n t e r m e d i a t e s must be i n c h l s s m a t l c n u c l e u s (SCL). S k u l l o p e n i n g s were made w i t h a d e n t a l c r e a s e d , and we have found t h a t brown f a t m i t o c h o n d r i a d r i l l i n o r d e r to p o s i t i o n t h e e l e c t r o d e s i n t h e s u p r a p o s s e s s an e f f i c i e n t p y r u v a t e c a r b o x y l a s e which, d u r i n g c h i a s m a t l c n u c l e i f o r t h e i r l e s l o n l n s ( 0 . 5 mm a n t e r i o r to t h e r m o g e n e s l s , can s y n t h e s i z e o x a l o a c e t a t e as a condensing bregma; L-O, D-8 u below s k u l l s u r f a c e ) o r f o r i n s e r t i o n of p a r t n e r for a c e t y l - C o A . By t h i s r e a c t i o n it is thus p o s s i b l e t h e e l e c t r o d e w i t h o u t p a s s i n g c u r r a n t in o r d e r to produce to i n c r e a s e the r a t e o f e n e r g y d i s s i p a t i o n i n brown f a t . c o n t r o l (SL) a n i m a l s , w l t h same c o o r d i n a t e s a s above, e x c e p t d a p t h w a s 7 m below s k u l l s u r f a c e ; second, s e v e r a l weeks later, for laplantlng sensors for temperature monitoring (Aerospace Ned. 4 8 : 3 1 7 7 , 1 9 6 9 ) . For c h r o n o b l o l o g l c a l s e r i a l TEMPERATURE-INDUCE~ CHANGES IN THE METABOLITE PATTERN UPON s e c t i o n s ( I n t . J . o f Cbronoblology 1 : 3 1 , 1973) a 24-h c o s i n e NOREPINEPHRINE STIMULATION OF HAMSTER BROWN ADIPOCYTES. c u r v e was f i t t e d by l e a s t s q u a r e s to 4 8 - h d a t a s e c t i o n s , th e Vlbeke S.M. Bernson, Per Lundberg and B e r t l l P e t t e r s s o n , October 7, 1977, A f t e r n o o n
97
The Wenner--Gren l o s t l t u t e , U n i v e r s i t y of Stockholm, N o r r tullsgatan 16, S-I13 45 Stockholm, Sweden. At low t e m p e r a t u r e a c e t a t e has been d e ~ n s t r a t e d to be a major e n d - p r o d u c t o f f a t t y a c i d o x i d a t i o n i n brown a d i p o s e t i s s u e m l t o c h o n d r i a from h a m s t e r s . In i s o l a t e d brown a d i p o VOLUNTARY C O NT R IB UTI ONS ON "THERMOGENESIS c y t e s n o r e p i n e p h r i n e (NE) i s t h e n a t u r a l th e r mo g e n ic e f f e c t o r which s t i m u l a t e s l i p o l y s i s and i n c r e a s e oxygen consumption. F r e e f a t t y a c i d s can r e p l a c e NE a s a s t i m u l a t o r o f AND TEMPERATURE REGULATION" oxygen consumption. The aim o f our i n v e s t i g a t i o n i s to study to what e x t e n t t h e f r e e f a t t y a c i d - i n d u c e d r e s p i r a t i o n i n C h a i r m a n : W i l l i a m R. D a w s o n ( U n i v e r s i t y of M i c h i g a n ) i s o l a t e d hamster brown s d i p o c y t e s r e p r e s e n t e d p r o d u c t i o n o f c i t r i c a c i d c y c l e i n t e r m e d i a t e s and a c e t a t e . As t h e hamster, a h i b e r n a t o r , can v a r y i t s body t e m p e r a t u r e between about CENTRAL AND PERIPHERAL INTERACTIONS IN THE CONTROL OF TRER38"C and 5"C, the temperature dependence of these pathways was investigated. Isolated brown adipocytes were incubated MOGENESIS. E. Z e i a b e r g e r , Zentrum fur P h y s i o l o g i e , J u s t u s i n K r e b s - g l n g e r - p h o s p h a t e - b u f f e r (KRPB) i n an oxygen e l e c L l e b l g - U n i v e r s l t g t Gle~sen, Aulweg 129, D-63 Gtessen. t r o d e chamber and oxygen consumption was measured a s a f u n c An e s s e n t i a l f e a t u r e o f a c u t e c o l d exposure i s t h e a c t i t i o n of added NE or palmitic acid. Halo,ate was used to test v a t i o n of the p e r i p h e r a l s y m p a t h e t i c system. The n o r a d r e n a to what extent the rate of oxygen consumption was dependent l i n e (NA) l i b e r a t e d from t h i s system r e d u c e s h e a t l o s s and promotes heat p r o d u c t i o n mechanisms. NA i s a l s o known to I n - on the citric acid cycle. At 370C in KRPB bubbled with 5Z f l u e n c e the hypothalamic thermoregulatory centers. The mean CO 2 in air the maximal oxygen consumption upon NE stimulabody temperature at which guinea plgs start to shiver (~b-Sh) tion was 490 nmol O2/mln x 106 cells, of which about 75% represents th e citric acid cycle, and 23%, which cannot be inhas been found to be increased after an intrahypothalamic hibited by ~alonate, represents fatty acid oxidation s t o p p (i.h.) mlcroinJection o f NA and d e c r e a s e d a f t e r i . h . a p p l i in g a t th e a c e t y l - C o A l e v e l . At 30°C 50% r e p r e s e n t s th e c i c a t i o n of an o-adrenerglc b l o c k e r (Zeisberger & BrUck: PflUt r i c acid cycle and 50% th e acetyl-level, while at 2O°C as gets Arch. 362, 113, 1976). Electrical stimulation of the much as 77% of the maximal NE-inducible oxygen consumption lower brain stem at sites presumed to be parts of the asr a t e r e p r e s e n t s end p r o d u c t s a t t h e a c e t y l - l e v e l . Acetate cending catecholamlnerglc pathways (ACP) had the same effect l e v e l s in l i v i n g h a m s t e r s were measured by a n a l y s i n g blood as i . h . NA m i c r o i n J e c t i o n ( S z e l ~ n y l e t a Z . : P f l U g e r s Arch. samples w i t h an enzymatic a s s a y i n a s p e c t r o p h o t o m e t e r . The 364, 123, 1976). The s e n s i t i v i t y to i.h. NA microlnJection acetate concentration in blood from warm-adapted, cold-adapwas h i g h e r in c o l d a d a p t e d (CA) and i n newborn (NB) t h a n in warm a d a p t e d (WA) g u i n e a p i g s . The s e n s i t i v i t y to i . h . phen- ted and h i b e r n a t i n g h a m s t e r s were i n th e mmolar r a n g e , w i t h These d a t a t o l a m i n e i n j e c t i o n s was r e c i p r o c a l l y r e l a t e d . T h i s i n d i c a t e s the highest values found in hibernating animals t o g e t h e r with o ld literature references reporting gQ-values t h a t t h e a c t i v i t y in t h e ACP Is h i g h e r in WA than i n CA or i n NB a n i m a l s . By c o n t r a s t t h e p e r i p h e r a l r e l e a s e of NA i s lower than 0.7 measured during hibernation could indicate i n c r e a s e d i n CA a n i m a l s exposed t o c o l d and i s g r e a t e r in NB that acetate is an important "end" product in brown adipose tissue during hibernation and/or arousal from hlbernat Ion. a n i m a l s than in WA a n i m a l s even a t n e u t r a l t e m p e r a t u r e . In o r d e r t o answer t h e q u e s t i o n whether t h e NA r e l e a s e d p e r i p h e r a l l y i n f l u e n c e s t h e n e u r a l a c t i v i t y i n t h e ACP, the p e r i p h e r a l NA level in NA guinea pigs was increased by i.m. NA ULTKASTRUCTURAL DEMONSTRATIONOF A UNILOCULAR TO MULTIi n f u s i o n ( 1 . 3 mE/ks • h) l a s t i n g 2 h r s and t h e e f f e c t on LOCULAR TRANSFORMATIONOF ADIPOCYTES IN DEVELOPING HAMSTER T b - S h w a s studied. The Tb-Sh was lowered by I"C as early as INTERSCAPULAR ADIPOSE TISSUE. POSSIBLE ROLE OF THE 15 minutes after the beginning of the infusion. After the SYMPATHETIC INNERVATION. Myriam N~chad. The Wenner-Gren infusion the Tb-Sh remained low for at least 3 hours. By contrast i.m. infusion of adrenaline increased the~b-Sh. It Institute, University of Stockholm, Norrtullsgatan 16, S-I13 45 Stockholm, Sweden. is concluded that the high peripheral NA level supresses the During the development of Interscapular adipose tissue a c t i v i t y in the ACP by some negative feedback mechanism. in the hamster, the adipocytes are first not multi- but Thlscould be the basic mechanism of the cold-adaptive shift unilocular. The development of the multilocularity does of Tb-Sh. not start before shout 4 days pos~ p~tt#~and is complete by 15 days post pa~-~um. We have investigated this process by e l e c t r o n m i c r o s c o p y , n o r e p l n e p h r i n e d e t e r m i n a t i o n s and light microscopic autoradlography. We o b s e r v e d two diffBROWN ADIPOSE TISSUE AND NON-SHIVERING THERMOGENESIS Barbara Cannon, Jan Nedergaard, Ulf Sundin and Olv erentiatlon pathways occurring simultaneously: (I) formL t n d b e r g . The Wenner-Gren I n s t i t u t e , U n i v e r s i t y o f ation o f m u l t i l o c u l a r a d i p o c y t e p r e c u r s o r c e l l s from Stockholm, N o r r t u l l s g a t a n 16, $-113 45 Stockholm, e n d o t h e l i a l c e l l s as p r e v i o u s l y d e s c r i b e d ; (2) d i r e c t Sweden. transformation of uni- into m u l t i l o c u l a r adlpocytes By mlcrocalorimetric measurements we have recently showing th e same c h a r a c t e r i s t i c development of th e chondd e m o n s t r a t e d chat t h e h e a t i n g c a p a c i t y of brown f a t in rlome a s in pathway ( I ) and f o r m a t i o n of s m a l l f a t d r o p l e t s h a m s t e r s i s low when c a l c u l a t e d on t h e b a s i s o f t h e whole i n th e p e r i p h e r a l c y t o p l a s m . By 12-15 d a y s , the u l t r a a n i m a l . N o n e t h e l e s s , t h e r e i s an e x t r e m e l y h i g h oxygen c o n structure of these cells has become indlstlnguishable from sumption in the t i s s u e and t h e r e f o r e c o n s i d e r a b l e l o c a l those formed via (1). Such direct transformation of white heat evolution. The high rate of oxygen utilisation rei n t o brown f a t h a s been r e p o r t e d i n a d u l t human p e r i r e n a l quires either a high ATP synthesizing capacity Of the mltofat i n association with e.g. s e v e r e chronic hypoxemia chondrla together with a high rate of ATP hydrolysis oP and pheochromacytoma. In the developing hamster brown fat, a loosening of coupling between oxygen consumption and ATP i t o c c u r s p a r a l l e l w i t h a marked i n c r e a s e i n t i s s u e n o r synthesis. We have demonstrated in isolated mitochondrla epinephrine concentration. The d e n s i t y o f s y m p a t h e t i c that an ATP syntheslsin K system which could parallel the n e r v e f i b r e s i s b e i n g i n v e s t i g a t e d by l i g h t m i c r o s c o p i c r e s p i r a t o r y a c t i v i t y found d u r i n g t h e r m o g e n e s i s i s not p r e sutoradiography. s e n t in brown f a t m i t o c h o n d r i a from h a m s t e r . Instead, a l o o s e n i n g of c o u p l i n g i s r e q u i r e d which i n some manner seems to involve c y t o p l a s m i c p u r l n e n u c l e o t i d e s ( e g . GDP). SUPRACRIASMATIC DINUCLEAR LESION ALTERS CIRCADIAN TEMPERATURE When GDP i s bound t o a s p e c i f i c membrane p r o t e i n o f i s o l a R H Y T ~ ' S AMPLITUDE AND TIMING IN LIGHT-DARK SYNCHRONIZED RATS. t e d , uncoupled m i t o c h o n d r i a , they become c a p a b l e o f e n e r g y P o w e l l , E . N . , J . N . P a s l e y , B. Brockway, L.E. S c h e v i n g , W. Luconservation. In t h e thermogenic c e l l acyl-CoA w i l l be p r o b a n o v ic and F. H a l b e r g . U n i v e r s i t i e s o f M i n n e s o t a , M i n n e a p o l i s , duced and we have shown t h a t low c o n c e n t r a t i o n s o f p a l m i M i n n . , 55455, and A r k a n s a s , L i t t l e Rock, 72201, USA toyl-CoA c a n remove GDP from its m i t o c h o n d r i a l b i n d i n g s i t e . I n t r a p e r l t o n e a l t e m p e r a t u r e was t e l e m e t e r e d (Space L i f e T h i s a c t i o n would f a c i l i t a t e a loosening of coupling. The S c i e n c e 2 : 4 3 7 , 1971) a t l O ' - I n t e r v a l s f o r 9 days from young a p p a r e n t Km f o r o x i d a t i o n of acyl-CoA i s h i g h so i t i s f e a a d u l t male i n b r e d F i s h e r r a t s k e p t a t 24 ± l ' C e n v i r o n m e n t a l s i b l e t o t h i n k t h a t e l e v a t e d acyl-CoA c o n c e n t r a t i o n s can t e m p e r a t u r e w i t h food and w a t e r f r e e l y a v a i l a b l e , s i n g l y i n be found a t l e a s t l o c a l l y . When e n t r y i n t o the c i t r i c a c i d c a g e s measuring 6 ' ~ x 5"H x 10'% i n l i g h t ( a p p r o x l m a t e l y 25 c y c l e i s l i m i t i n g ( e g . due to l a c k of c o n d e n s i n g p a r t n e r ) l u x ) and d a r k n e s s a l t e r n a t i n g e v e r y 1 2 - h (LD 1 2 : 1 2 ) . The r a t s acyl-CoA combustion w i l l o n l y p r e c e e d t h r o u g h ~ - o x i d a t i o n had been o p e r a t e d upon under a n e s t h e s i a t w i c e , f i r s t f o r to t h e a c e t y l l e v e l . High r a t e s o f o x i d a t i o n demand t h a t p l a c i n g s t e r e o t a x l c a l l y an e l e c t r o l y t i c l e s i o n o f t h e s u p r a t h e l e v e l of c i t r i c a c i d c y c l e i n t e r m e d i a t e s must be i n c h l s s m a t l c n u c l e u s (SCL). S k u l l o p e n i n g s were made w i t h a d e n t a l c r e a s e d , and we have found t h a t brown f a t m i t o c h o n d r i a d r i l l i n o r d e r to p o s i t i o n t h e e l e c t r o d e s i n t h e s u p r a p o s s e s s an e f f i c i e n t p y r u v a t e c a r b o x y l a s e which, d u r i n g c h i a s m a t l c n u c l e i f o r t h e i r l e s l o n l n s ( 0 . 5 mm a n t e r i o r to t h e r m o g e n e s l s , can s y n t h e s i z e o x a l o a c e t a t e as a condensing bregma; L-O, D-8 u below s k u l l s u r f a c e ) o r f o r i n s e r t i o n of p a r t n e r for a c e t y l - C o A . By t h i s r e a c t i o n it is thus p o s s i b l e t h e e l e c t r o d e w i t h o u t p a s s i n g c u r r a n t in o r d e r to produce to i n c r e a s e the r a t e o f e n e r g y d i s s i p a t i o n i n brown f a t . c o n t r o l (SL) a n i m a l s , w l t h same c o o r d i n a t e s a s above, e x c e p t d a p t h w a s 7 m below s k u l l s u r f a c e ; second, s e v e r a l weeks later, for laplantlng sensors for temperature monitoring (Aerospace Ned. 4 8 : 3 1 7 7 , 1 9 6 9 ) . For c h r o n o b l o l o g l c a l s e r i a l TEMPERATURE-INDUCE~ CHANGES IN THE METABOLITE PATTERN UPON s e c t i o n s ( I n t . J . o f Cbronoblology 1 : 3 1 , 1973) a 24-h c o s i n e NOREPINEPHRINE STIMULATION OF HAMSTER BROWN ADIPOCYTES. c u r v e was f i t t e d by l e a s t s q u a r e s to 4 8 - h d a t a s e c t i o n s , th e Vlbeke S.M. Bernson, Per Lundberg and B e r t l l P e t t e r s s o n , October 7, 1977, A f t e r n o o n