Abstract
White adipose tissue (WAT) has important dual energy-storage and endocrine functions, which become deranged in obesity, contributing to the pathogenesis of inflammatory metabolic disorders such as type-2 diabetes. Humans express SCD1 in WAT, and rodents express both SCD1 and SCD2 in this tissue. WAT SCD expression is regulated by hormones, cytokines, and nutritional status. Leptin, estrogen, and tumor necrosis factor-alpha reduce its expression, while insulin and ghrelin increase it. In humans, hypercaloric or high-carbohydrate diets stimulate WAT SCD expression, while caloric restriction suppresses it. Fatty acids have differential effects on WAT SCD expression with polyunsaturated fatty acids (PUFAs) having an inhibitory effect and saturated fatty acids (SFAs) having a stimulatory effect. Interestingly, effects of peroxisome proliferator-activated receptor gamma agonists are species-specific. WAT SCD plays an important role in modulating metabolic functions. Its expression positively correlates with body weight and insulin resistance. Although germline SCD1 deletion protects mice from diet-induced obesity and insulin resistance, adipose-specific SCD knockout does not provide these protective effects. Therefore, it is likely that WAT SCD upregulation in obesity is an adaption to increased availability of carbohydrates and SFAs. However, since palmitoleate and oleate, two major products of the desaturation reaction catalyzed by this enzyme, regulate inflammatory responses, WAT SCD also appears to be important in modulating adipose tissue inflammation in obesity. In conclusion, SCD is an important enzyme for triglyceride storage of WAT, which has additional functions in regulating metabolism and inflammation, especially in conditions of expanded fat mass.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Boden G, Duan X, Homko C, Molina EJ, Song W, Perez O, Cheung P, Merali S (2008) Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 57:2438–2444
Bryzgalova G, Lundholm L, Portwood N, Gustafsson JA, Khan A, Efendic S, Dahlman-Wright K (2008) Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice. Am J Physiol Endocrinol Metab 295:E904–E912
Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS (2008) Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134:933–944
Choi Y, Kim YC, Han YB, Park Y, Pariza MW, Ntambi JM (2000) The trans-10, cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. J Nutr 130:1920–1924
Chong MF, Hodson L, Bickerton AS, Roberts R, Neville M, Karpe F, Frayn KN, Fielding BA (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr 87:817–823
Christianson JL, Nicoloro S, Straubhaar J, Czech MP (2008) Stearoyl-CoA desaturase 2 is required for peroxisome proliferator-activated receptor gamma expression and adipogenesis in cultured 3T3-L1 cells. J Biol Chem 283:2906–2916
Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgins LC, Ntambi JM, Friedman JM (2002) Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297:240–243
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939
Franck N, Gummesson A, Jernas M, Glad C, Svensson PA, Guillot G, Rudemo M, Nystrom FH, Carlsson LM, Olsson B (2011) Identification of adipocyte genes regulated by caloric intake. J Clin Endocrinol Metab 96:E413–E418
Frick F, Linden D, Ameen C, Eden S, Mode A, Oscarsson J (2002) Interaction between growth hormone and insulin in the regulation of lipoprotein metabolism in the rat. Am J Physiol Endocrinol Metab 283:E1023–E1031
Gallardo N, Bonzon-Kulichenko E, Fernandez-Agullo T, Molto E, Gomez-Alonso S, Blanco P, Carrascosa JM, Ros M, Andres A (2007) Tissue-specific effects of central leptin on the expression of genes involved in lipid metabolism in liver and white adipose tissue. Endocrinology 148:5604–5610
Gong J, Campos H, McGarvey S, Wu Z, Goldberg R, Baylin A (2011a) Adipose tissue palmitoleic acid and obesity in humans: does it behave as a lipokine? Am J Clin Nutr 93:186–191
Gong J, Campos H, McGarvey S, Wu Z, Goldberg R, Baylin A (2011b) Genetic variation in stearoyl-CoA desaturase 1 is associated with metabolic syndrome prevalence in Costa Rican adults. J Nutr 141:2211–2218
Hegele RA (2001) Molecular basis of partial lipodystrophy and prospects for therapy. Trends Mol Med 7:121–126
Hyun CK, Kim ED, Flowers MT, Liu X, Kim E, Strable M, Ntambi JM (2010) Adipose-specific deletion of stearoyl-CoA desaturase 1 up-regulates the glucose transporter GLUT1 in adipose tissue. Biochem Biophys Res Commun 399:480–486
Jaudszus A, Moeckel P, Hamelmann E, Jahreis G (2010) Trans-10, cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation. Ann Nutr Metab 57:103–111
Jiang G, Li Z, Liu F, Ellsworth K, Dallas-Yang Q, Wu M, Ronan J, Esau C, Murphy C, Szalkowski D, Bergeron R, Doebber T, Zhang BB (2005) Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1. J Clin Invest 115:1030–1038
Johansson LE, Danielsson AP, Parikh H, Klintenberg M, Norstrom F, Groop L, Ridderstrale M (2012) Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. Am J Clin Nutr 96:196–207
Jones BH, Maher MA, Banz WJ, Zemel MB, Whelan J, Smith PJ, Moustaid N (1996) Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased by polyunsaturated fatty acids. Am J Physiol 271:E44–E49
Jones BH, Standridge MK, Claycombe KJ, Smith PJ, Moustaid-Moussa N (1998) Glucose induces expression of stearoyl-CoA desaturase in 3T3-L1 adipocytes. Biochem J 335(Pt 2):405–408
Kaestner KH, Ntambi JM, Kelly TJ Jr, LANE MD (1989) Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase. J Biol Chem 264:14755–14761
Kalupahana NS, Moustaid-Moussa N (2012a) The adipose tissue renin-angiotensin system and metabolic disorders: a review of molecular mechanisms. Crit Rev Biochem Mol Biol 47:379–390
Kalupahana NS, Moustaid-Moussa N (2012b) The renin-angiotensin system: a link between obesity, inflammation and insulin resistance. Obes Rev 13:136–149
Kalupahana NS, Claycombe KJ, Moustaid-Moussa N (2011) (n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: mechanistic insights. Adv Nutr 2:304–316
Kalupahana NS, Massiera F, Quignard-Boulange A, Ailhaud G, Voy BH, Wasserman DH, Moustaid-Moussa N (2012a) Overproduction of angiotensinogen from adipose tissue induces adipose inflammation, glucose intolerance, and insulin resistance. Obesity (Silver Spring) 20:48–56
Kalupahana NS, Moustaid-Moussa N, Claycombe KJ (2012b) Immunity as a link between obesity and insulin resistance. Mol Aspects Med 33:26–34
Kim YC, Gomez FE, Fox BG, Ntambi JM (2000) Differential regulation of the stearoyl-CoA desaturase genes by thiazolidinediones in 3T3-L1 adipocytes. J Lipid Res 41:1310–1316
Kurebayashi S, Hirose T, Miyashita Y, Kasayama S, Kishimoto T (1997) Thiazolidinediones downregulate stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. Diabetes 46:2115–2118
Lin J, Choi YH, Hartzell DL, Li C, Della-Fera MA, Baile CA (2003) CNS melanocortin and leptin effects on stearoyl-CoA desaturase-1 and resistin expression. Biochem Biophys Res Commun 311:324–328
Liu X, Miyazaki M, Flowers MT, Sampath H, Zhao M, Chu K, Paton CM, Joo DS, Ntambi JM (2010) Loss of stearoyl-CoA desaturase-1 attenuates adipocyte inflammation: effects of adipocyte-derived oleate. Arterioscler Thromb Vasc Biol 30:31–38
Lundholm L, Zang H, Hirschberg AL, Gustafsson JA, Arner P, Dahlman-Wright K (2008) Key lipogenic gene expression can be decreased by estrogen in human adipose tissue. Fertil Steril 90:44–48
Macek Jilkova Z, Pavelka S, Flachs P, Hensler M, Kus V, Kopecky J (2010) Modulation of type I iodothyronine 5'-deiodinase activity in white adipose tissue by nutrition: possible involvement of leptin. Physiol Res 59:561–569
Mainieri D, Montani JP, Seydoux J, Giacobino JP, Boss O, Dulloo AG (2007) beta-Adrenergic control of stearoyl-CoA desaturase 1 repression in relation to sympathoadrenal regulation of thermogenesis. Int J Obes (Lond) 31:378–381
Mangravite LM, Dawson K, Davis RR, Gregg JP, Krauss RM (2007) Fatty acid desaturase regulation in adipose tissue by dietary composition is independent of weight loss and is correlated with the plasma triacylglycerol response. Am J Clin Nutr 86:759–767
Matsubara Y, Kano K, Kondo D, Mugishima H, Matsumoto T (2009) Differences in adipocytokines and fatty acid composition between two adipocyte fractions of small and large cells in high-fat diet-induced obese mice. Ann Nutr Metab 54:258–267
Mauvoisin D, Mounier C (2011) Hormonal and nutritional regulation of SCD1 gene expression. Biochimie 93:78–86
Nagare T, Sakaue H, Matsumoto M, Cao Y, Inagaki K, Sakai M, Takashima Y, Nakamura K, Mori T, Okada Y, Matsuki Y, Watanabe E, Ikeda K, Taguchi R, Kamimura N, Ohta S, Hiramatsu R, Kasuga M (2011) Overexpression of KLF15 transcription factor in adipocytes of mice results in down-regulation of SCD1 protein expression in adipocytes and consequent enhancement of glucose-induced insulin secretion. J Biol Chem 286:37458–37469
Nikonova L, Koza RA, Mendoza T, Chao PM, Curley JP, Kozak LP (2008) Mesoderm-specific transcript is associated with fat mass expansion in response to a positive energy balance. FASEB J 22:3925–3937
Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920
Ntambi JM, Buhrow SA, Kaestner KH, Christy RJ, Sibley E, Kelly TJ Jr, Lane MD (1988) Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. J Biol Chem 263:17291–17300
Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci U S A 99:11482–11486
Okada T, Furuhashi N, Kuromori Y, Miyashita M, Iwata F, Harada K (2005) Plasma palmitoleic acid content and obesity in children. Am J Clin Nutr 82:747–750
Pasarica M, Rood J, Ravussin E, Schwarz JM, Smith SR, Redman LM (2010) Reduced oxygenation in human obese adipose tissue is associated with impaired insulin suppression of lipolysis. J Clin Endocrinol Metab 95:4052–4055
Pinnick KE, Neville MJ, Fielding BA, Frayn KN, Karpe F, Hodson L (2012) Gluteofemoral adipose tissue plays a major role in production of the lipokine palmitoleate in humans. Diabetes 61:1399–1403
Sampath H, Miyazaki M, Dobrzyn A, Ntambi JM (2007) Stearoyl-CoA desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J Biol Chem 282:2483–2493
Sessler AM, Kaur N, Palta JP, Ntambi JM (1996) Regulation of stearoyl-CoA desaturase 1 mRNA stability by polyunsaturated fatty acids in 3T3-L1 adipocytes. J Biol Chem 271:29854–29858
Shea J, French CR, Bishop J, Martin G, Roebothan B, Pace D, Fitzpatrick D, Sun G (2009) Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese men. Am J Clin Nutr 89:407–415
Sjogren P, Sierra-Johnson J, Gertow K, Rosell M, Vessby B, de Faire U, Hamsten A, Hellenius ML, Fisher RM (2008) Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance. Diabetologia 51:328–335
Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schurmann A, Szanto I, Tschop MH, Rohner-Jeanrenaud F (2006) Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 116:1983–1993
Turyn J, Stojek M, Swierczynski J (2010) Up-regulation of stearoyl-CoA desaturase 1 and elongase 6 genes expression in rat lipogenic tissues by chronic food restriction and chronic food restriction/refeeding. Mol Cell Biochem 345:181–188
Wang Z, Nakayama T (2010) Inflammation, a link between obesity and cardiovascular disease. Mediators Inflamm 2010:535918
Weiner FR, Smith PJ, Wertheimer S, Rubin CS (1991) Regulation of gene expression by insulin and tumor necrosis factor alpha in 3T3-L1 cells. Modulation of the transcription of genes encoding acyl-CoA synthetase and stearoyl-CoA desaturase-1. J Biol Chem 266:23525–23528
Yao-Borengasser A, Rassouli N, Varma V, Bodles AM, Rasouli N, Unal R, Phanavanh B, Ranganathan G, McGehee RE Jr, Kern PA (2008) Stearoyl-coenzyme A desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-gamma responsiveness. J Clin Endocrinol Metab 93:4431–4439
Yee JK, Phillips SA, Allamehzadeh K, Herbst KL (2012) Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders. Lipids Health Dis 11:19
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kalupahana, N.S., Jayalath, T., Wang, S., Moustaid-Moussa, N. (2013). Regulation and Metabolic Functions of White Adipose Tissue Stearoyl-CoA Desaturase. In: Ntambi, Ph.D., J. (eds) Stearoyl-CoA Desaturase Genes in Lipid Metabolism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7969-7_5
Download citation
DOI: https://doi.org/10.1007/978-1-4614-7969-7_5
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-7968-0
Online ISBN: 978-1-4614-7969-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)