Skip to main content
SpringerLink
Log in

Hepatic BSCL2 (Seipin) Deficiency Disrupts Lipid Droplet Homeostasis and Increases Lipid Metabolism via SCD1 Activity

  • Original Article
  • Published:
Lipids

Abstract

Berardinelli-Seip congenital lipodystrophy (BSCL) is an autosomal recessive disorder. The more severe form, designated BSCL2, arises due to mutations in the BSCL2 gene. Patients with BSCL2, as well as Bscl2 −/− mice, have a near total absence of body fat, an organomegaly, and develop metabolic disorders including insulin resistance and hepatic steatosis. The function of the Seipin (BSCL2) protein remains poorly understood. Several lines of evidence have indicated that Seipin may have distinct functions in adipose versus non-adipose cells. Here we present evidence that BSCL2/Bscl2 plays a role in lipid droplet (LD) biogenesis and homeostasis in primary and cultured hepatocytes. Our results show that decreasing BSCL2/Bscl2 expression in hepatocytes increases the number and size of LD, as well as the expression of genes implicated in their formation and stability. We also show that knocking down SCD1 expression reverses the phenotype associated with Seipin deficiency. Interestingly, BSCL2 knockdown induces SCD1 expression and activity, potentially leading to increased basal phosphorylation of proteins involved in the insulin signaling cascade, as well as further increasing fatty acid uptake and de novo lipogenesis. In conclusion, our results suggest that a hepatic BSCL2/Bscl2 deficiency induces the increase and expansion of LD, potentially via increased SCD1 activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ACC:

Acetyl-CoA carboxylase

AGPAT:

1-Acylglycerol-3-phosphate O-acyltransferases

ATGL:

Adipose triglyceride lipase

ATF6:

Activating transcription factor-6

ANOVA:

Analysis of variance

BSCL:

Berardinelli-Seip congenital lipodystrophy

BSA:

Bovine serum albumin

CIDEA:

Cell death-inducing DFFA-like effector a

CE:

Cholesteryl esters

DAG:

Diacylglycerol

PERK:

Double-stranded RNA-dependent protein kinase-like ER kinase

ER:

Endoplasmic reticulum

FAS:

Fatty acid synthase

FRQNT:

Fond de Recherche du Québec-Nature et Technologie

G6pc:

Glucose-6-phosphatase catalytic subunit

Gck:

Glucokinase

GRP78:

Glucose-regulated protein 78

GTT:

Glucose tolerance test

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HPRT1:

Hypoxanthine phosphoribosyltransferase 1

IRE1a:

Inositol-requiring transmembrane kinase and endonuclease 1a

IRS:

Insulin receptor substrate

ITT:

Insulin tolerance test

KO:

Knockout

LD:

Lipid droplet

mTOR:

Mechanistic target of rapamycin

MUFA:

Monounsaturated fatty acids

NSERC:

National Science and Engineering Research Council of Canada

NASH:

Non-alcoholic steatohepatitis

PPAR:

Peroxisome proliferator activated receptor

PLIN5:

Perilipin 5

Pepck:

Phosphoenolpyruvate carboxykinase

PBS:

Phosphate-buffered saline

PL:

Phospholipids

SFA:

Saturated fatty acids

SREBP-1c:

Sterol regulatory element binding protein-1c

SCD1:

Stearoyl-CoA desaturase 1

TAG:

Triacylglycerol

FFA:

Unesterified fatty acids

UPR:

Unfolded protein response

WT:

Wildtype

References

  1. Garg A (2011) Clinical review#: lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab 96(11):3313–3325

    Article  CAS  PubMed  Google Scholar 

  2. Berardinelli W (1954) An undiagnosed endocrinometabolic syndrome: report of 2 cases. J Clin Endocrinol Metab 14(2):193–204

    Article  CAS  PubMed  Google Scholar 

  3. Seip M (1959) Lipodystrophy and gigantism with associated endocrine manifestations. A new diencephalic syndrome? Acta Paediatr 48:555–574

    CAS  PubMed  Google Scholar 

  4. Agarwal AK, Garg A (2004) Seipin: a mysterious protein. Trends Mol Med 10(9):440–444

    Article  CAS  PubMed  Google Scholar 

  5. Magre J et al (2001) Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet 28(4):365–370

    Article  CAS  PubMed  Google Scholar 

  6. Agarwal AK, Garg A (2003) Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways. Trends Endocrinol Metab 14(5):214–221

    Article  CAS  PubMed  Google Scholar 

  7. Cui X et al (2011) Seipin ablation in mice results in severe generalized lipodystrophy. Hum Mol Genet 20(15):3022–3030

    Article  CAS  PubMed  Google Scholar 

  8. Prieur X et al (2013) Thiazolidinediones partially reverse the metabolic disturbances observed in Bscl2/seipin-deficient mice. Diabetologia 56(8):1813–1825

    Article  CAS  PubMed  Google Scholar 

  9. Chen W et al (2012) Berardinelli-seip congenital lipodystrophy 2/seipin is a cell-autonomous regulator of lipolysis essential for adipocyte differentiation. Mol Cell Biol 32(6):1099–1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Payne VA et al (2008) The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation. Diabetes 57(8):2055–2060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu L et al (2014) Adipose-specific knockout of SEIPIN/BSCL2 results in progressive lipodystrophy. Diabetes 63(7):2320–2331

    Article  PubMed  Google Scholar 

  12. Unger RH (2002) Lipotoxic diseases. Annu Rev Med 53:319–336

    Article  CAS  PubMed  Google Scholar 

  13. van Herpen NA, Schrauwen-Hinderling VB (2008) Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 94(2):231–241

    Article  PubMed  Google Scholar 

  14. Szendroedi J, Roden M (2009) Ectopic lipids and organ function. Curr Opin Lipidol 20(1):50–56

    Article  CAS  PubMed  Google Scholar 

  15. Gao M et al (2015) Expression of seipin in adipose tissue rescues lipodystrophy, hepatic steatosis and insulin resistance in seipin null mice. Biochem Biophys Res Commun 460(2):143–150

    Article  CAS  PubMed  Google Scholar 

  16. Chen W et al (2014) Molecular mechanisms underlying fasting modulated liver insulin sensitivity and metabolism in male lipodystrophic Bscl2/Seipin-deficient mice. Endocrinology 155(11):4215–4225

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cartwright BR, Goodman JM (2012) Seipin: from human disease to molecular mechanism. J Lipid Res 53(6):1042–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fei W, Du X, Yang H (2011) Seipin, adipogenesis and lipid droplets. Trends Endocrinol Metab 22(6):204–210

    Article  CAS  PubMed  Google Scholar 

  19. Fei W et al (2008) Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast. J Cell Biol 180(3):473–482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wolinski H et al (2011) A role for seipin in lipid droplet dynamics and inheritance in yeast. J Cell Sci 124(Pt 22):3894–3904

    Article  CAS  PubMed  Google Scholar 

  21. Wolinski H et al (2015) Seipin is involved in the regulation of phosphatidic acid metabolism at a subdomain of the nuclear envelope in yeast. Biochim Biophys Acta 1851(11):1450–1464

    Article  CAS  PubMed  Google Scholar 

  22. Wang CW, Miao YH, Chang YS (2014) Control of lipid droplet size in budding yeast requires the collaboration between Fld1 and Ldb16. J Cell Sci 127(Pt 6):1214–1228

    Article  PubMed  Google Scholar 

  23. Fei W et al (2011) A role for phosphatidic acid in the formation of “supersized” lipid droplets. PLoS Genet 7(7):e1002201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Szymanski KM et al (2007) The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc Natl Acad Sci USA 104(52):20890–20895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fei W et al (2011) Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis. J Lipid Res 52(12):2136–2147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tian Y et al (2011) Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation. PLoS Genet 7(4):e1001364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yang W et al (2013) Seipin differentially regulates lipogenesis and adipogenesis through a conserved core sequence and an evolutionarily acquired C-terminus. Biochem J 452(1):37–44

    Article  CAS  PubMed  Google Scholar 

  28. Harris CA et al (2011) DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes. J Lipid Res 52(4):657–667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Brasaemle DL, Wolins NE (2012) Packaging of fat: an evolving model of lipid droplet assembly and expansion. J Biol Chem 287(4):2273–2279

    Article  CAS  PubMed  Google Scholar 

  30. Talukder MM et al (2015) Seipin oligomers can interact directly with AGPAT2 and lipin 1, physically scaffolding critical regulators of adipogenesis. Mol Metab 4(3):199–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yang W et al (2014) BSCL2/seipin regulates adipogenesis through actin cytoskeleton remodelling. Hum Mol Genet 23(2):502–513

    Article  CAS  PubMed  Google Scholar 

  32. Bi J et al (2014) Seipin promotes adipose tissue fat storage through the ER Ca(2)(+)-ATPase SERCA. Cell Metab 19(5):861–871

    Article  CAS  PubMed  Google Scholar 

  33. Puri P et al (2008) Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology 134(2):568–576

    Article  CAS  PubMed  Google Scholar 

  34. Puri V et al (2007) Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage. J Biol Chem 282(47):34213–34218

    Article  CAS  PubMed  Google Scholar 

  35. Fang DL et al (2013) Endoplasmic reticulum stress leads to lipid accumulation through upregulation of SREBP-1c in normal hepatic and hepatoma cells. Mol Cell Biochem 381(1–2):127–137

    Article  CAS  PubMed  Google Scholar 

  36. Rinella ME et al (2011) Dysregulation of the unfolded protein response in db/db mice with diet-induced steatohepatitis. Hepatology 54(5):1600–1609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gentile CL, Frye M, Pagliassotti MJ (2011) Endoplasmic reticulum stress and the unfolded protein response in nonalcoholic fatty liver disease. Antioxid Redox Signal 15(2):505–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang XQ et al (2014) Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 20(7):1768–1776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhang K et al (2011) The unfolded protein response transducer IRE1alpha prevents ER stress-induced hepatic steatosis. EMBO J 30(7):1357–1375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang C et al (2012) Endoplasmic reticulum-tethered transcription factor cAMP responsive element-binding protein, hepatocyte specific, regulates hepatic lipogenesis, fatty acid oxidation, and lipolysis upon metabolic stress in mice. Hepatology 55(4):1070–1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rutkowski DT, Kaufman RJ (2004) A trip to the ER: coping with stress. Trends Cell Biol 14(1):20–28

    Article  CAS  PubMed  Google Scholar 

  42. Harbrecht BG et al (2001) cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding activity in cultured rat hepatocytes. J Surg Res 99(2):258–264

    Article  CAS  PubMed  Google Scholar 

  43. Harbrecht BG et al (1996) Glucagon inhibits hepatocyte nitric oxide synthesis. Arch Surg 131(12):1266–1272

    Article  CAS  PubMed  Google Scholar 

  44. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917

    Article  CAS  PubMed  Google Scholar 

  45. Ralston JC et al (2014) Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis. Int J Obes (Lond) 38(11):1449–1456

    Article  CAS  Google Scholar 

  46. Fernandez C et al (2011) Altered desaturation and elongation of fatty acids in hormone-sensitive lipase null mice. PLoS One 6(6):e21603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Attie AD et al (2002) Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J Lipid Res 43(11):1899–1907

    Article  CAS  PubMed  Google Scholar 

  48. Stremmel W, Berk PD (1986) Hepatocellular influx of [14C]oleate reflects membrane transport rather than intracellular metabolism or binding. Proc Natl Acad Sci USA 83(10):3086–3090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pohl J, Ring A, Stremmel W (2002) Uptake of long-chain fatty acids in HepG2 cells involves caveolae: analysis of a novel pathway. J Lipid Res 43(9):1390–1399

    Article  CAS  PubMed  Google Scholar 

  50. Bolker HI et al (1956) The incorporation of acetate-1-C14 into cholesterol and fatty acids by surviving tissues of normal and scorbutic guinea pigs. J Exp Med 103(2):199–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Jin FY, Kamanna VS, Kashyap ML (1999) Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells. Arterioscler Thromb Vasc Biol 19(4):1051–1059

    Article  CAS  PubMed  Google Scholar 

  52. Jiang M et al (2014) Lack of testicular seipin causes teratozoospermia syndrome in men. Proc Natl Acad Sci USA 111(19):7054–7059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wu L et al (2014) Cidea controls lipid droplet fusion and lipid storage in brown and white adipose tissue. Sci China Life Sci 57(1):107–116

    Article  CAS  PubMed  Google Scholar 

  54. Wang H et al (2011) Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J Lipid Res 52(12):2159–2168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Beller M et al (2008) COPI complex is a regulator of lipid homeostasis. PLoS Biol 6(11):e292

    Article  PubMed  PubMed Central  Google Scholar 

  56. Guo Y et al (2008) Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature 453(7195):657–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Soni KG et al (2009) Coatomer-dependent protein delivery to lipid droplets. J Cell Sci 122(Pt 11):1834–1841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. He J et al (2011) The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Exp Biol Med (Maywood) 236(10):1116–1121

    Article  CAS  Google Scholar 

  59. Cheon Y et al (2005) Induction of overlapping genes by fasting and a peroxisome proliferator in pigs: evidence of functional PPARalpha in nonproliferating species. Am J Physiol Regul Integr Comp Physiol 288(6):R1525–R1535

    Article  CAS  PubMed  Google Scholar 

  60. Louet JF et al (2001) Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor alpha (PPARalpha)-independent pathway. Biochem J 354(Pt 1):189–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Berardinelli SD, Fischer RM, Katz I (1956) Congenital absence of the pectoral muscle. Am J Roentgenol Radium Ther Nucl Med 76(3):599–604

    CAS  PubMed  Google Scholar 

  62. Thomas SE et al (2010) Diabetes as a disease of endoplasmic reticulum stress. Diabetes Metab Res Rev 26(8):611–621

    Article  CAS  PubMed  Google Scholar 

  63. Kaufman RJ (2002) Orchestrating the unfolded protein response in health and disease. J Clin Invest 110(10):1389–1398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lee JS et al (2012) Pharmacologic ER stress induces non-alcoholic steatohepatitis in an animal model. Toxicol Lett 211(1):29–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chen W et al (2009) The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation. Endocrinology 150(10):4552–4561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim MS et al (2014) A draft map of the human proteome. Nature 509(7502):575–581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lundin C et al (2006) Membrane topology of the human seipin protein. FEBS Lett 580(9):2281–2284

    Article  CAS  PubMed  Google Scholar 

  68. Ntambi JM et al (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99(17):11482–11486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Walther TC, Farese RV Jr (2009) The life of lipid droplets. Biochim Biophys Acta 1791(6):459–466

    Article  CAS  PubMed  Google Scholar 

  70. Novikoff AB et al (1980) Organelle relationships in cultured 3T3-L1 preadipocytes. J Cell Biol 87(1):180–196

    Article  CAS  PubMed  Google Scholar 

  71. Perktold A et al (2007) Organelle association visualized by three-dimensional ultrastructural imaging of the yeast cell. FEMS Yeast Res 7(4):629–638

    Article  CAS  PubMed  Google Scholar 

  72. Ito D, Suzuki N (2009) Seipinopathy: a novel endoplasmic reticulum stress-associated disease. Brain 132(Pt 1):8–15

    PubMed  Google Scholar 

  73. Yagi T et al (2011) N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress. Hum Mol Genet 20(19):3831–3840

    Article  CAS  PubMed  Google Scholar 

  74. Holtta-Vuori M et al (2013) Alleviation of seipinopathy-related ER stress by triglyceride storage. Hum Mol Genet 22(6):1157–1166

    Article  PubMed  Google Scholar 

  75. Shi X et al (2013) Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase. J Lipid Res 54(9):2504–2514

    Article  PubMed  PubMed Central  Google Scholar 

  76. Arisawa K et al (2013) Changes in the phospholipid fatty acid composition of the lipid droplet during the differentiation of 3T3-L1 adipocytes. J Biochem 154(3):281–289

    Article  CAS  PubMed  Google Scholar 

  77. Miyazaki M et al (2007) Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab 6(6):484–496

    Article  CAS  PubMed  Google Scholar 

  78. Man WC et al (2006) Colocalization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis. J Lipid Res 47(9):1928–1939

    Article  CAS  PubMed  Google Scholar 

  79. Kim E et al (2011) Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro. Eur J Pharmacol 672(1–3):38–44

    Article  CAS  PubMed  Google Scholar 

  80. Chen W et al (2014) Molecular mechanisms underlying fasting modulated liver insulin sensitivity and metabolism in male lipodystrophic Bscl2/Seipin-deficient mice. Endocrinology p. en20141292

  81. Coll T et al (2008) Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J Biol Chem 283(17):11107–11116

    Article  CAS  PubMed  Google Scholar 

  82. Nardi F et al (2014) Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A. PLoS One 9(3):e92255

    Article  PubMed  PubMed Central  Google Scholar 

  83. Xiao C et al (2006) Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans. Diabetologia 49(6):1371–1379

    Article  CAS  PubMed  Google Scholar 

  84. Vessby B et al (2001) Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study. Diabetologia 44(3):312–319

    Article  CAS  PubMed  Google Scholar 

  85. Salvado L et al (2013) Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism. Diabetologia 56(6):1372–1382

    Article  CAS  PubMed  Google Scholar 

  86. O’Brien RM, Granner DK (1996) Regulation of gene expression by insulin. Physiol Rev 76(4):1109–1161

    PubMed  Google Scholar 

  87. Mendez-Lucas A et al (2014) Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) is a pro-survival, endoplasmic reticulum (ER) stress response gene involved in tumor cell adaptation to nutrient availability. J Biol Chem 289(32):22090–22102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Foufelle F, Ferre P (2002) New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 366(Pt 2):377–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Foretz M et al (1998) AMP-activated protein kinase inhibits the glucose-activated expression of fatty acid synthase gene in rat hepatocytes. J Biol Chem 273(24):14767–14771

    Article  CAS  PubMed  Google Scholar 

  90. Zhou G et al (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108(8):1167–1174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Decaux JF, Antoine B, Kahn A (1989) Regulation of the expression of the L-type pyruvate kinase gene in adult rat hepatocytes in primary culture. J Biol Chem 264(20):11584–11590

    CAS  PubMed  Google Scholar 

  92. Prip-Buus C et al (1995) Induction of fatty-acid-synthase gene expression by glucose in primary culture of rat hepatocytes. Dependency upon glucokinase activity. Eur J Biochem 230(1):309–315

    Article  CAS  PubMed  Google Scholar 

  93. O’Callaghan BL et al (2001) Glucose regulation of the acetyl-CoA carboxylase promoter PI in rat hepatocytes. J Biol Chem 276(19):16033–16039

    Article  PubMed  Google Scholar 

  94. Koo SH, Dutcher AK, Towle HC (2001) Glucose and insulin function through two distinct transcription factors to stimulate expression of lipogenic enzyme genes in liver. J Biol Chem 276(12):9437–9445

    Article  CAS  PubMed  Google Scholar 

  95. Waters KM, Ntambi JM (1994) Insulin and dietary fructose induce stearoyl-CoA desaturase 1 gene expression of diabetic mice. J Biol Chem 269(44):27773–27777

    CAS  PubMed  Google Scholar 

  96. Foufelle F et al (1992) Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. J Biol Chem 267(29):20543–20546

    CAS  PubMed  Google Scholar 

  97. Jones BH et al (1998) Glucose induces expression of stearoyl-CoA desaturase in 3T3-L1 adipocytes. Biochem J 335(Pt 2):405–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We wish to thank Dr. Jocelyne Magre (University of Nantes, France) for kindly providing us with mRNA and protein extracts from Bscl2 −/− mice, as well as Dr. Xiaoqin Ye (University of Georgia, USA) for samples of Bscl2 −/− mouse liver. We also thank Denis Flipo for his precious help with confocal microscopy, the laboratory of Dr. Diana Averill for primary rat hepatocytes, and Dr. Daniel Boismenu for his help with data analysis and discussion. The Discovery Grants Program of the National Science and Engineering Research Council of Canada (NSERC) funded this research. MAL and SL were supported by the Fond de Recherche du Québec-Nature et Technologie (FRQNT) fellowships.

Author information

Authors and Affiliations

  1. Département des sciences biologiques et centre de recherche BioMed, Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, QC, H3C 3P8, Canada

    Mohamed Amine Lounis, Simon Lalonde, Sabri Ahmed Rial, Karl-F. Bergeron & Catherine Mounier

  2. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada

    Jessica C. Ralston & David M. Mutch

Authors
  1. Mohamed Amine Lounis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon Lalonde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sabri Ahmed Rial
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karl-F. Bergeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jessica C. Ralston
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David M. Mutch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Catherine Mounier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catherine Mounier.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lounis, M.A., Lalonde, S., Rial, S.A. et al. Hepatic BSCL2 (Seipin) Deficiency Disrupts Lipid Droplet Homeostasis and Increases Lipid Metabolism via SCD1 Activity. Lipids 52, 129–150 (2017). https://doi.org/10.1007/s11745-016-4210-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-016-4210-5

Keywords

Search

Navigation