Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment

Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and palmitoleate. Mice with a targeted disruption of the SCD1 isoform (SCD1−/−) exhibit reduced adiposity and increased energy expenditure. To address whether the energy expenditure is attributable to increased thermogenesis, we investigated the effect of SCD1 deficiency on basal and cold-induced thermogenesis. SCD1−/− mice have increased expression of uncoupling proteins in brown adipose tissue (BAT) relative to controls. The β3-adrenergic receptor (β3-AR) expression was increased and the phosphorylation of cAMP response element binding protein and the protein level of peroxisome proliferator-activated receptor-γ coactivator-1α were increased in the SCD1−/− mice. Both lipolysis and fatty acid oxidation were increased in the SCD1−/− mice. When exposed to 4°C, SCD1−/− mice showed hypothermia, hypoglycemia, and depleted liver glycogen. High levels of dietary oleate partially compensated for the hypothermia and rescued plasma glucose and liver glycogen.These results suggest that SCD1 deficiency stimulates basal thermogenesis through the upregulation of the β3-AR-mediated pathway and a subsequent increase in lipolysis and fatty acid oxidation in BAT. The hypothermia and hypoglycemia in cold-exposed SCD1−/− mice and the compensatory recovery by oleate indicate an important role of SCD1 gene expression in thermoregulation. Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and palmitoleate. Mice with a targeted disruption of the SCD1 isoform (SCD1−/−) exhibit reduced adiposity and increased energy expenditure. To address whether the energy expenditure is attributable to increased thermogenesis, we investigated the effect of SCD1 deficiency on basal and cold-induced thermogenesis. SCD1−/− mice have increased expression of uncoupling proteins in brown adipose tissue (BAT) relative to controls. The β3-adrenergic receptor (β3-AR) expression was increased and the phosphorylation of cAMP response element binding protein and the protein level of peroxisome proliferator-activated receptor-γ coactivator-1α were increased in the SCD1−/− mice. Both lipolysis and fatty acid oxidation were increased in the SCD1−/− mice. When exposed to 4°C, SCD1−/− mice showed hypothermia, hypoglycemia, and depleted liver glycogen. High levels of dietary oleate partially compensated for the hypothermia and rescued plasma glucose and liver glycogen. These results suggest that SCD1 deficiency stimulates basal thermogenesis through the upregulation of the β3-AR-mediated pathway and a subsequent increase in lipolysis and fatty acid oxidation in BAT. The hypothermia and hypoglycemia in cold-exposed SCD1−/− mice and the compensatory recovery by oleate indicate an important role of SCD1 gene expression in thermoregulation. Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. It catalyzes the introduction of the cis double bond in the Δ9 position of fatty acyl-CoA substrates. The major monounsaturated fatty acids of triglyceride (TG), cholesteryl esters, and membrane phospholipids are palmitoleic and oleic acids (1Sessler A.M. Ntambi J.M. Polyunsaturated fatty acid regulation of gene expression.J. Nutr. 1998; 128: 923-926Google Scholar). The ratio of stearic acid to oleic acid is one of the factors influencing cell membrane fluidity, and an alteration in this ratio is implicated in obesity, aging, and various diseases such as diabetes, heart disease, and cancer (2Clandinin M.T. Cheema S. Field C.J. Garg M.L. Benkatraman J. Clandinin T.R. Dietary fat: exogenous determination of membrane structure and cell function.FASEB J. 1991; 5: 2761-2769Google Scholar). Four SCD isoforms exist in the mouse genome. SCD1 is expressed in liver and brown and white adipose tissue, whereas SCD2 is expressed in brain and brown and white adipose tissue (3Ntambi J.M. The regulation of stearoyl-CoA desaturase (SCD).Prog. Lipid Res. 1995; 34: 139-150Google Scholar). SCD3 is expressed mainly in the skin and Harderian gland (4Ntambi J.M. Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol.J. Lipid Res. 1999; 40: 1549-1558Google Scholar), whereas SCD4 is expressed in heart (5Miyazaki M. Jacobson J.M. Man W.C. Cohen P. Asilmaz E. Friedman J.M. Ntambi J.M. Identification and characterization of murine SCD4: a novel heart-specific stearoyl CoA desaturase isoform regulated by leptin and dietary factor.J. Biol. Chem. 2003; 278: 33904-33911Google Scholar). Recent studies of the asebia mouse strains (ab j and ab 2j) with a naturally occurring mutation in SCD1 and a laboratory mouse model with a targeted disruption (SCD1−/−) provide new insights into the physiological role of the SCD1 gene and its endogenous products (6Zheng Y. Eilertsen K.J. Ge L. Zhang L. Sundberg J.P. Prouty S.M. Stenn K.S. Parimoo S. SCD1 is expressed in sebaceous glands and is disrupted in the asebia mouse.Nat. Genet. 1999; 23: 268-270Google Scholar, 7Miyazaki M. Kim Y. Ntambi J.M. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis.J. Lipid Res. 2001; 42: 1018-1024Google Scholar). Mice with a targeted disruption of the SCD1 gene had reduced adiposity. TG synthesis in liver was decreased relative to that in the wild type, which suggests that SCD1 gene expression is highly correlated with fat accumulation (7Miyazaki M. Kim Y. Ntambi J.M. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis.J. Lipid Res. 2001; 42: 1018-1024Google Scholar). The reduction in fat accumulation of SCD1−/− mice was the result of downregulation in the expression of lipogenic genes (FAS, SREBP1, GPAT) and upregulation in the expression of genes involved in fatty acid oxidation (8Ntambi J.M. Miyazaki M. Stoehr J.P. Lan H. Kendziorski C.M. Yandell B.S. Song Y. Cohen P. Friedman J.M. Attie A.D. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.Proc. Natl. Acad. Sci. USA. 2002; 99: 11482-11486Google Scholar). In addition, SCD1 deficiency decreased the obese phenotype of the ob/ob mouse (9Cohen P. Miyazaki M. Socci N.D. Hagge-Greenberg A. Liedtke W. Soukas A.A. Sharma R. Hudgins L.C. Ntambi J.M. Friedman J.M. Role of stearoyl-CoA desaturase-1 in leptin mediated weight loss.Science. 2002; 297: 240-243Google Scholar), suggesting that obesity is highly correlated with SCD1 expression. Energy expenditure is an important factor in the regulation of body weight. Heat production (thermogenesis) represents a major form of energy expenditure and plays a significant role in the maintenance of energy balance. Brown adipose tissue (BAT) is the primary site of thermogenesis and potentially functions to regulate body weight in rodents (10Lowell B.B. S-Susulic V. Hamann A. Lawitts J.A. Himms-Hagen J. Boyer B.B. Kozak L.P. Flier J.S. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue.Nature. 1993; 366: 740-742Google Scholar, 11Kopecky J. Hodny Z. Rossmeisl M. Syrovy I. Kozak L.P. Reduction of dietary obesity in aP2-UCP transgenic mice: physiology and adipose tissue distribution.Am. J. Physiol. 1996; 270: E768-E775Google Scholar). Therefore, enhanced function of BAT is a significant factor that increases energy expenditure and reduces obesity. Uncoupling protein 1 (UCP1) is predominantly expressed in BAT of rodents and functions to uncouple oxidative respiration from ATP synthesis, resulting in dissipation of energy as heat (12Ricquier D. Bouillaud F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP.Biochem. J. 2000; 345: 161-179Google Scholar). The UCP1 gene in BAT is activated in response to cold exposure and plays a part in the maintenance of body temperature, as demonstrated in UCP1 knockout mice that showed cold sensitivity and lower oxygen consumption (13Enerback S. Jacobsson A. Simpson E.M. Guerra C. Yamashita H. Harper M.E. Kozak L.P. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese.Nature. 1997; 387: 90-94Google Scholar, 14Matthias A. Ohlson K.B.E. Fredriksson J.M. Jacobsson A. Nedergaard J. Cannon B. Thermogenic responses in brown fat cells are fully UCP-1 dependent.J. Biol. Chem. 2000; 275: 25073-25081Google Scholar). Two structurally homologous UCPs, UCP2 and UCP3, have been identified in BAT of rodents (15Fleury C. Neverova M. Collins S. Raimbault S. Champigny O. Levi-Meyrueis C. Bouillaud F. Seldin M.F. Surwit R.S. Ricquier D. Warden C.H. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.Nat. Genet. 1997; 15: 269-272Google Scholar, 16Boss O. Samec S. Paoloni-Giacobino A. Rossier C. Dulloo A. Seydoux J. Muzzin P. Giacobino J.P. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression.FEBS Lett. 1997; 408: 39-42Google Scholar); however, their role in nonshivering thermogenesis remains unclear (14Matthias A. Ohlson K.B.E. Fredriksson J.M. Jacobsson A. Nedergaard J. Cannon B. Thermogenic responses in brown fat cells are fully UCP-1 dependent.J. Biol. Chem. 2000; 275: 25073-25081Google Scholar). Recently, there has been growing interest in the role of β3-adrenergic receptor (β3-AR) because of its predominant expression in adipose tissue and potential as a pharmacological target to control energy expenditure and lipid accretion (17Bachman E.S. Dhillon H. Zhang C-Y. Cinti S. Bianco A. Kobilka B.K. Lowell B.B. β-AR signaling required for diet-induced thermogenesis and obesity resistance.Science. 2002; 297: 843-845Google Scholar). Pharmacological studies indicate that the β-AR subtype responsible for the stimulation of oxygen consumption and UCP expression is exclusively the β3 subtype (18Zhao J. Cannon B. Nedergaard J. Thermogenesis is beta3 but not beta1-adrenergically mediated in rat brown fat cells, even after cold acclimation.Am. J. Physiol. 1998; 275: R2002-R2011Google Scholar). Stimulation of β3-ARs leads to nonshivering thermogenesis via the activation of in brown fat S. Surwit R.S. The and the control of adipose tissue and Res. 2001; Scholar). is to the and stimulates subsequent responses through via protein A S. Surwit R.S. The and the control of adipose tissue and Res. 2001; Scholar), which cAMP response element binding protein H. Fredriksson J.M. Nedergaard J. Cannon B. A novel pathway for stimulation of element binding protein via and protein J. 2002; and M.F. activation of brown and cAMP production in the mouse by 1995; Scholar). the is that fatty acids as for mitochondrial oxidation and provide a to UCP1 J. V. A. A. Jacobsson A. Cannon B. the protein to thermogenesis and 2001; Scholar). acids the and UCP1 expression in brown even the physiological is (14Matthias A. Ohlson K.B.E. Fredriksson J.M. Jacobsson A. Nedergaard J. Cannon B. Thermogenic responses in brown fat cells are fully UCP-1 dependent.J. Biol. Chem. 2000; 275: 25073-25081Google Scholar, J. A. lipolysis and respiration in rat brown The role of fatty acids as of mitochondrial respiration and of Biol. Chem. Scholar, A. Jacobsson A. Cannon B. Nedergaard J. The of brown fat from Biol. Chem. 1999; Scholar). In a we have that SCD1 knockout mice have enhanced oxygen consumption and (8Ntambi J.M. Miyazaki M. Stoehr J.P. Lan H. Kendziorski C.M. Yandell B.S. Song Y. Cohen P. Friedman J.M. Attie A.D. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.Proc. Natl. Acad. Sci. USA. 2002; 99: 11482-11486Google Scholar). the physiological role and of SCD1 deficiency in has not been The of the was to whether deficiency of SCD1 the of BAT. that SCD1 deficiency increased basal thermogenesis through the activation of a β3-AR-mediated pathway and subsequent increases in lipolysis and fatty acid oxidation in BAT of mice. cold SCD1−/− mice hypothermia, which is with hypoglycemia and of liver glycogen. Dietary oleate partially for hypothermia and hypoglycemia in cold-exposed SCD1−/− suggesting that oleate plays a role in the control of with and lipid The of targeted SCD1−/− mice has been M. Man W.C. Ntambi J.M. disruption of stearoyl-CoA desaturase 1 gene in mice of sebaceous and glands and of in the Nutr. 2001; Scholar). (SCD1−/−) and mice on a were The and of is in with the by the of the of Mice were on a and were a diet of and SCD1−/− mice were control diet by for and exposed to for The diet was from and and for UCP1 and were from and for and peroxisome proliferator-activated receptor-γ coactivator-1α were from and were from and were from were from was from BAT with to the of was on and to the membrane was with with by a the were exposed to and were by on an The were for UCP1 Y. M. M. Uncoupling is a of thermogenesis regulated by and Biol. Chem. 1997; Scholar), UCP2 Y. M. M. Uncoupling is a of thermogenesis regulated by and Biol. Chem. 1997; Scholar), and S. O. B. C.J. C. Kozak L.P. C. C. Harper M.L. of obesity and response to and in mice lacking uncoupling Biol. Chem. 2000; 275: Scholar). The for and were by the for and for and BAT was in and and for The proteins were by to and by for UCP1, and The proteins were the enhanced as by the and by were as by synthesis in a membrane with Biol. Chem. Scholar). 1 was as by J. The effect of on the of liver and its by Scholar). A of of mitochondrial protein was to and for the was by of acid for the was with of in of and with of of was by acid oxidation was as by J. and fatty acid oxidation in liver and from control and Biol. Chem. with BAT was in and for The was for the The of and with in The was by the and the for The was by 1 of by The was with 1 of to The of the was The protein was with the protein as a were from BAT to the of and A of lipid and J. Biol. Chem. Physiol. Scholar). of and phospholipids BAT was and the were with of the was and and in of The were by acid as a The were from the and by as (7Miyazaki M. Kim Y. Ntambi J.M. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis.J. Lipid Res. 2001; 42: 1018-1024Google Scholar). BAT cells were from brown fat from and SCD1−/− as M. P. C. P. Nedergaard J. Cannon B. Development of brown fat cells in and from white fat cells in Res. Scholar). BAT was in and for The brown were in an of in and the of with and brown were in for and was with and with for the was to a glucose was a and was as S. of in tissue Physiol. Scholar). was with with To whether SCD1 deficiency basal we UCP expression in BAT from SCD1−/− and mice. that UCP1 levels were increased by in SCD1−/− mice relative to mice UCP2 and levels were increased in SCD1−/− mice by and relative to levels as a control were not with the increased the UCP1 protein level was in SCD1−/− mice in mice In is responsible for the regulation of the the protein A and the activation of UCP1 S. Surwit R.S. The and the control of adipose tissue and Res. 2001; Scholar). To whether the in the upregulation of in the and protein levels of were SCD1−/− and mice. The and protein levels of were and in SCD1−/− mice relative to mice. The and levels by were not by SCD1 deficiency not The factor gene expression via and protein A to UCP1 expression J.S. Kozak L.P. for protein and factors in the of the mitochondrial uncoupling protein 1 Biol. Chem. 2002; Scholar). To whether is activated by phosphorylation in SCD1−/− we the levels of in BAT by an against which the protein stimulates gene by phosphorylation of Scholar). in the level of in BAT of SCD1−/− mice was increased by relative to controls. The was not by SCD1 deficiency not of UCP1 is a of implicated in thermogenesis and mitochondrial The are mediated through the β3-adrenergic pathway P. proliferator-activated receptor-γ and 2003; Scholar, P. Z. R. M. A of linked to 1998; Scholar). To whether is responsible for increased UCP1 we and protein levels in BAT of SCD1−/− and mice. The protein level was increased by in SCD1−/− mice relative to mice the level was not by SCD1 deficiency not activated lipolysis in adipose tissue and lipolysis is to to the activation of UCP1 in we expression to whether upregulation of results from increased lipolysis in BAT of SCD1−/− mice. The level was increased by in BAT of SCD1−/− mice relative to mice In showed that increased by in brown from SCD1−/− mice relative to from mice the of the in expression in BAT and the increased in lipolysis in the brown from SCD1−/− we whether the of and were by SCD1 deficiency in BAT. TG were decreased by and in BAT of SCD1−/− mice. The was decreased by in SCD1−/− mice and plasma of SCD1−/− mice was lower that of mice The was increased by in SCD1−/− mice. The fatty acid in was to whether SCD1 deficiency fatty acid in BAT. the relative of the major fatty acids from In the TG SCD1−/− mice had an in relative of and a in oleate In the and the relative of and decreased in SCD1−/− mice. The of monounsaturated fatty acids were by significant increases in the of the fatty acids and The of SCD1−/− mice showed and in and the of and were increased in the of SCD1−/− and were in the of fatty and in and TG in BAT and liver and after cold exposure for TG TG TG brown adipose stearoyl-CoA desaturase 1 SCD1−/− mice. in a new fatty acid of and in BAT from and SCD1−/− in a new brown adipose stearoyl-CoA desaturase 1 SCD1−/− mice. The of in BAT and plasma suggests that fatty acid oxidation increased in BAT of SCD1−/− mice. To whether fatty acid oxidation is increased in BAT of SCD1−/− we BAT level and as as the of fatty acid oxidation in of BAT. level and were increased in BAT of SCD1−/− mice by and relative to mice The of fatty acid oxidation was in BAT of SCD1−/− mice relative to that of mice To whether deficiency of the SCD1 gene in a cold a was temperature, the was not SCD1−/− and mice of cold exposure 4°C, SCD1−/− mice showed cold and of the SCD1−/− mice their body decreased to whereas mice and their body the These results suggest that SCD1 plays a significant role in cold-induced thermogenesis and that to body in of cold are not in SCD1−/− mice. has been that thermogenesis is mediated by UCP1 and that its expression is by cold UCP1 level was after a exposure of SCD1−/− and mice in cold exposure increased UCP1 level in as as SCD1−/− mice. the was in mice in SCD1−/− which suggests that UCP1 is expressed in and SCD1−/− mice after cold cold a in is by heat production via thermogenesis. Thermogenesis is mainly by and whereas the of protein oxidation remains To SCD1−/− mice hypothermia 4°C, we plasma glucose in cold-exposed SCD1−/− and mice. glucose level was not SCD1−/− and mice however, glucose level was decreased by in SCD1−/− mice after of cold exposure plasma glucose level is by we in liver of SCD1−/− and mice after cold temperature, liver was not SCD1−/− and mice. after cold liver of SCD1−/− mice was decreased by and was depleted relative to that of mice These results suggest that the of and glucose to the hypothermia in SCD1−/− mice exposed to In a cold cold by lipid and heat production W. the of fatty acid synthesis and in murine brown adipose from gene expression and in J. 2002; Scholar, E. F. B. R. D. C. in from J. Physiol. Physiol. 2002; Scholar). To whether cold exposure fat in and the of TG was in plasma TG is lower in SCD1−/− relative to mice exposure decreased plasma TG in and SCD1−/− mice by and was decreased in SCD1−/− mice relative to mice exposure decreased plasma in mice by plasma was increased by in SCD1−/− mice. BAT and liver TG was decreased in SCD1−/− mice relative to mice cold BAT and liver TG was increased by and in mice. TG was not in the BAT and liver of SCD1−/− mice. oleate is the primary of SCD1 gene expression and is by of exogenous from the we investigated whether dietary of to the mice for the hypothermia in cold-exposed SCD1−/− mice. was as a control for the SCD1−/− mice the diet decreased body relative to mice SCD1−/− mice the diet showed body and after cold exposure relative to SCD1−/− mice the the body to Dietary not body in mice cold To whether UCP1 we UCP1 levels in BAT of and SCD1−/− mice. UCP1 levels were not in SCD1−/− mice To whether recovery of body by is with plasma glucose and liver levels were Dietary increased plasma glucose and liver in SCD1−/− mice by and but not plasma glucose and liver to the levels in mice. TG was to whether dietary fat accumulation in BAT and in of levels of dietary increased the TG of BAT and liver of and SCD1−/− mice. The TG levels in liver and BAT of SCD1−/− were not increased to the levels in in BAT and liver after in cold-exposed and SCD1−/− TG TG of and SCD1−/− mice were a control a diet of fatty for and exposed to for SCD1−/− mice. in a new of and SCD1−/− mice were a control a diet of fatty for and exposed to for SCD1−/− mice. Mice with a targeted disruption of the SCD1 isoform are against diet-induced have increased energy and expression of genes of fatty acid The SCD1−/− mice exhibit of oxygen consumption their the and In this we and that of SCD1 stimulates basal thermogenesis and the β3-AR-mediated pathway in BAT. SCD1 deficiency increased lipolysis and fatty acid oxidation in BAT. the SCD1−/− mice were exposed to a cold to increase thermogenesis increased expression of The mice hypothermia and hypoglycemia, an important role of SCD1 gene expression in thermoregulation. The of increased UCP1 expression in BAT of SCD1−/− mice is The results suggest that the activation of the signaling that and protein expression were increased in SCD1−/− mice. The increase in expression was by increased activation of which is the primary factor of β3-AR-mediated in BAT. on the of in response to activation the of the UCP1 gene J.S. Kozak L.P. for protein and factors in the of the mitochondrial uncoupling protein 1 Biol. Chem. 2002; Scholar, stimulates gene by phosphorylation of Scholar). levels of protein in BAT the activation of UCP1 expression in SCD1−/− mice because proliferator-activated receptor peroxisome proliferator-activated receptor acid and that to the UCP1 and indicate that a major of the cAMP effect is mediated by P. proliferator-activated receptor-γ and 2003; Scholar, P. Z. R. M. A of linked to 1998; Scholar). The and levels were not and SCD1−/− suggesting that SCD1 deficiency the activation of by its phosphorylation and expression a The increased expression of and the reduction in levels of TG and suggest increased lipolysis in BAT of SCD1−/− mice. The plasma fatty acid levels to the of in BAT and in the plasma was decreased in SCD1−/− mice. The increased gene expression and enzyme as as the increased oxidation of acid provide of the oxidation in BAT of SCD1−/− mice. that SCD1 deficiency cold-induced thermogenesis because SCD1 deficiency in BAT we that SCD1−/− mice showed hypothermia after of cold UCP1 was not responsible for cold-induced hypothermia in SCD1−/− mice. in the cold on increased energy expenditure and from the energy liver and adipose that SCD1−/− mice had reduced levels of liver which suggests that SCD1−/− mice mice for thermogenesis. The and BAT was not decreased in SCD1−/− mice cold exposure not suggests that liver plays a role in and to a level of glucose in the of the is for energy the increase in lipid cold exposure is a to increase in the of the maintenance of heat production for a and of in the cold F. F. D. C. C. J.M. of cold exposure on in plasma and Physiol. 2002; Scholar). cold a increase of in tissue such as BAT and liver after cold suggesting that is an of cold W. the of fatty acid synthesis and in murine brown adipose from gene expression and in J. 2002; Scholar, E. F. B. R. D. C. in from J. Physiol. Physiol. 2002; Scholar). a in TG and an increase in plasma level in SCD1−/− mice after cold The reduced and reduced lipid in SCD1−/− mice responsible for the reduced heat production in the of Therefore, we the that dietary oleate in body by TG synthesis in SCD1−/− mice cold results showed that levels of dietary oleate partially rescued the deficiency of and TG in liver of SCD1−/− mice Dietary not the TG deficiency in the of SCD1−/− mice not These results the that and TG levels in liver of SCD1−/− mice by the of with results (7Miyazaki M. Kim Y. Ntambi J.M. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis.J. Lipid Res. 2001; 42: 1018-1024Google Scholar). not the that cold in the plasma membrane of SCD1−/− mice after cold exposure because SCD1−/− mice cold sensitivity and after of cold lipid ratio of to fatty membrane and A. M. Y. membrane lipid sensitivity and membrane lipid of and 2000; Scholar). In on the role of SCD1 deficiency in the and the of basal thermogenesis. in of the SCD1 gene the from activation to phosphorylation of and activation of which the activation of The resulting increase in lipolysis in SCD1−/− mice provide the for mitochondrial oxidation and the stimulation of UCP1 expression and basal thermogenesis. These result in increased energy expenditure and reduction in adiposity. SCD1 deficiency hypothermia, which is with hypoglycemia after cold The hypothermia and hypoglycemia in cold-exposed SCD1−/− mice and the compensatory recovery by dietary oleate suggest a significant role of SCD1 gene expression in which is with and lipid was by of and β3-adrenergic receptor brown adipose tissue cAMP response element binding protein acid peroxisome proliferator-activated receptor-γ coactivator-1α stearoyl-CoA desaturase triglyceride uncoupling protein