Skip to main content
SpringerLink
Log in

Effect of Fabp1/Scp-2/Scp-x Ablation on Whole Body and Hepatic Phenotype of Phytol-Fed Male Mice

  • Original Article
  • Published:
Lipids

Abstract

Liver fatty acid binding protein (Fabp1) and sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) genes encode proteins that enhance hepatic uptake, cytosolic transport, and peroxisomal oxidation of toxic branched-chain fatty acids derived from dietary phytol. Since male wild-type (WT) mice express markedly higher levels of these proteins than females, the impact of ablating both genes (TKO) was examined in phytol-fed males. In WT males, high phytol diet alone had little impact on whole body weight and did not alter the proportion of lean tissue mass (LTM) versus fat tissue mass (FTM). TKO conferred on dietary phytol the ability to induce weight loss as well as reduce liver weight, FTM, and even more so LTM. Concomitantly TKO induced hepatic lipid accumulation, preferentially threefold increased phospholipid (PL) at the expense of decreased triacylglycerol (TG) and total cholesterol. Increased PL was associated with upregulation of membrane fatty acid transport/translocase proteins (FATP 2,4), cytosolic fatty acid/fatty acyl-CoA binding proteins (FABP2, ACBP), and the rate limiting enzyme in PL synthesis (Gpam). Decreased TG and cholesterol levels were not attributable to altered levels in respective synthetic enzymes or nuclear receptors. These data suggest that the higher level of Fabp1 and Scp2/Scpx gene products in WT males was protective against deleterious effects of dietary phytol, but TKO significantly exacerbated phytol effects in males.

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

Similar content being viewed by others

Abbreviations

ACAT2:

Acyl-CoA cholesterol acyltransferase-2

ACBP:

Acyl-CoA-binding protein

Agpat2 :

1-Acylglycerol-3-phosphate-O-acyltransferase-2

apoA1:

Apolipoprotein A-I

apoB:

Apolipoprotein B

BSEP:

Bile salt export pump

BW:

Body weight

C:

Free cholesterol

cholesterol-E:

Cholesteryl ester

COX4:

Cytochrome c oxidase subunit IV

CPT1a or 2:

Carnitine palmitoyltransferase 1a or 2

CRABP I:

Cellular retinoic acid binding protein 1

DEXA:

Dual-energy X-ray absorptiometry

Dgat2 :

Diacylglycerol acyltransferase

FABP1:

Liver fatty acid binding protein (L-FABP)

FABP2:

Intestinal fatty acid binding protein

FATP2, 4, and 5:

Fatty acid transport protein 2, 4 and 5

FTM:

Fat tissue mass

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GPAT/Gpam :

Glycerol-3-phosphate acyltransferase

GST:

Glutathione s-transferase

HDL-C:

High density lipoprotein cholesterol

3αHSD:

3alpha-hydroxysteroid reductase

β-OHB:

β-Hydroxybutyrate

LDL-R:

Low density lipoprotein receptor

Lpin2 :

Phosphatidate phosphatase (lipin-2)

LTM:

Lean tissue mass

LxR:

Liver x receptor

MDR:

Multidrug resistance protein

non-HDL-C:

Non-HDL cholesterol

Ntcp :

Sodium-taurocholate cotransporting polypeptide

Oatp1 or 2 :

Organic anion-transporting polypeptide 1 or 2

PL:

Phospholipid

PPARα:

Peroxisome proliferator activated receptor alpha

qRT-PCR:

Quantitative real-time polymerase chain reaction

RxRα:

Retinoid x receptor α

SCP-2:

Sterol carrier protein-2

SCP-x:

Sterol carrier protein-x

SEM:

Standard error of the mean

SR-B1:

Scavenger receptor class B member 1

SREBP1 and 2:

Sterol regulatory element-binding protein 1 and 2

TG:

Triglyceride/triacylglycerol

TKO:

Fabp1/Scp-2/Scp-x gene ablated mouse

WT:

Wild-type mouse

References

  1. Steinberg D (1990) In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1533–1550

  2. Steinberg D (1995) Refsums disease. In: Scriver CR, Beaudet AL, Sly WS, Vallee D (eds) The metabolic and molecular basis of inherited disease. McGraw-Hill, New York, pp 2351–2370

    Google Scholar 

  3. Atshaves BP, Martin GG, Hostetler HA, McIntosh AL, Kier AB, Schroeder F (2010) Liver fatty acid binding protein (L-FABP) and dietary obesity. J Nutr Biochem 21:1015–1032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gallegos AM, Atshaves BP, Storey SM, Starodub O, Petrescu AD, Huang H, McIntosh A, Martin G, Chao H, Kier AB, Schroeder F (2001) Gene structure, intracellular localization, and functional roles of sterol carrier protein-2. Prog Lipid Res 40:498–563

    Article  CAS  PubMed  Google Scholar 

  5. Kannenberg F, Ellinghaus P, Assmann G, Seedorf U (1999) Aberrant oxidation of the cholesterol side chain in bile acid synthesis of sterol carrier protein-2/sterol carrier protein-x knockout mice. J Biol Chem 274:35455–35460

    Article  CAS  PubMed  Google Scholar 

  6. Monnig G, Wiekowski J, Kirchhof P, Stypmann J, Plenz G, Fabritz L, Bruns H-J, Eckardt L, Assmann G, Haverkamp W, Breithardt G, Seedorf U (2004) Phytanic acid accumulation is associated with conduction delay and sudden cardiac death in sterol carrier protein-2/sterol carrier protein-x deficient mice. J Cardiovasc Electrophysiol 15:1310–1316

    Article  PubMed  Google Scholar 

  7. Seedorf U, Ellinghaus P, Nofer JR (2000) Sterol carrier protein-2. Biochim Biophys Acta 1486:45–54

    Article  CAS  PubMed  Google Scholar 

  8. Frolov A, Miller K, Billheimer JT, Cho T-C, Schroeder F (1997) Lipid specificity and location of the sterol carrier protein-2 fatty acid binding site: a fluorescence displacement and energy transfer study. Lipids 32:1201–1209

    Article  CAS  PubMed  Google Scholar 

  9. Wolfrum C, Ellinghaus P, Fobker M, Seedorf U, Assmann G, Borchers T, Spener F (1999) Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein. J Lipid Res 40:708–714

    CAS  PubMed  Google Scholar 

  10. Atshaves BP, Storey SM, Petrescu AD, Greenberg CC, Lyuksyutova OI, Smith R, Schroeder F (2002) Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L-cell fibroblasts. Am J Physiol 283:C688–C703

    Article  CAS  Google Scholar 

  11. Atshaves BP, Storey S, Huang H, Schroeder F (2004) Liver fatty acid binding protein expression enhances branched-chain fatty acid metabolism. Mol Cell Biochem 259:115–129

    Article  CAS  PubMed  Google Scholar 

  12. Atshaves BP, McIntosh AL, Lyuksyutova OI, Zipfel WR, Webb WW, Schroeder F (2004) Liver fatty acid binding protein gene ablation inhibits branched-chain fatty acid metabolism in cultured primary hepatocytes. J Biol Chem 279:30954–30965

    Article  CAS  PubMed  Google Scholar 

  13. Antonenkov VD, Sormunen RT, Ohlmeier S, Amery L, Fransen M (2006) Localization of a portion of the liver isoform of fatty acid binding protein (L-FABP) to peroxisomes. Biochem J 394:475–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Atshaves BP, McIntosh AL, Payne HR, Mackie J, Kier AB, Schroeder F (2005) Effect of branched-chain fatty acid on lipid dynamics in mice lacking liver fatty acid binding protein gene. Am J Physiol 288:C543–C558

    Article  CAS  Google Scholar 

  15. Atshaves BP, McIntosh AL, Landrock D, Payne HR, Mackie J, Maeda N, Ball JM, Schroeder F, Kier AB (2007) Effect of SCP-x gene ablation on branched-chain fatty acid metabolism. Am J Physiol 292:939–951

    Google Scholar 

  16. Schroeder F, Frolov A, Schoer J, Gallegos A, Atshaves BP, Stolowich NJ, Scott AI, Kier AB (1998) Intracellular sterol binding proteins, cholesterol transport and membrane domains. In: Chang TY, Freeman DA (eds) Intracellular cholesterol trafficking. Kluwer Academic Publishers, Boston, pp 213–234

    Chapter  Google Scholar 

  17. Keller GA, Scallen TJ, Clarke D, Maher PA, Krisans SK, Singer SJ (1989) Subcellular localization of sterol carrier protein-2 in rat hepatocytes: its primary localization to peroxisomes. J Cell Biol 108:1353–1361

    Article  CAS  PubMed  Google Scholar 

  18. Martin GG, Hostetler HA, McIntosh AL, Tichy SE, Williams BJ, Russell DH, Berg JM, Spencer TA, Ball JA, Kier AB, Schroeder F (2008) Structure and function of the sterol carrier protein-2 (SCP-2) N-terminal pre-sequence. Biochem. 47:5915–5934

    Article  CAS  Google Scholar 

  19. Wouters F, Bastiaens PI, Wirtz KW, Jovin TM (1998) FRET microscopy demonstrates molecular association of non-specific lipid transfer protein (nsL-TP) with fatty acid oxidation enzymes. EMBO J 17:7179–7189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wanders RJ, Denis S, van Berkel E, Wouters F, Wirtz KWA, Seedorf U (1998) Identification of the newly discovered 58 kDa peroxisomal thiolase SCP-x as the main thiolase involved in both pristanic acid and trihydroyxycholestanoic acid oxidation: implications for peroxisomal beta-oxidation disorders. J Inherit Metab Dis 21:302–305

    Article  CAS  PubMed  Google Scholar 

  21. Wanders RJA, Denis S, Wouters F, Wirtz KWA, Seedorf U (1997) Sterol carrier protein X (SCPx) is a peroxisomal branched-chain b-ketothiolase specifically reacting with 3-oxo-pristanoyl-CoA: a new, unique role for SCPx in branched-chain fatty acid metabolism in peroxisomes. Biochem Biophys Res Commun 236:565–569

    Article  CAS  PubMed  Google Scholar 

  22. Seedorf U, Brysch P, Engel T, Schrage K, Assmann G (1994) Sterol carrier protein X is peroxisomal 3-oxoacyl coenzyme A thiolase with intrinsic sterol carrier and lipid transfer activity. J Biol Chem 269:21277–21283

    CAS  PubMed  Google Scholar 

  23. Antonenkov VD, Van Veldhoven PP, Waelkens E, Mannaerts GP (1997) Substrate specificities of 3-oxoacyl-CoA thiolase A and sterol carrier protein 2/3-oxoacyl-CoA thiolase purified from normal rat liver peroxisomes. J Biol Chem 272:26023–26031

    Article  CAS  PubMed  Google Scholar 

  24. Antonenkov VD, Van Veldhoven PP, Mannaerts GP (2000) Isolation and subunit composition of native sterol carrier protein-2/3-oxoacyl-coenzyme A thiolase from normal rat liver peroxisomes. Protein Exp. Purif 18:249–256

    Article  CAS  Google Scholar 

  25. Huang H, McIntosh AL, Martin GG, Landrock D, Chung S, Landrock KK, Dangott LJ, Li S, Kier AB, Schroeder F (2016) FABP1: a novel hepatic endocannabinoid and cannabinoid binding protein. Biochemistry 55:5243–5255

    Article  CAS  PubMed  Google Scholar 

  26. Atshaves BP, Payne HR, McIntosh AL, Tichy SE, Russell D, Kier AB, Schroeder F (2004) Sexually dimorphic metabolism of branched chain lipids in C57BL/6J mice. J Lipid Res 45:812–830

    Article  CAS  PubMed  Google Scholar 

  27. Klipsic D, Landrock D, Martin GG, McIntosh AL, Landrock KK, Mackie JT, Schroeder F, Kier AB (2015) Impact of SCP-2/SCP-x gene ablation and dietary cholesterol on hepatic lipid accumulation. Am J Physiol Gastrointest Liver Phys 309:G387–G399

    Article  CAS  Google Scholar 

  28. Seedorf U (1998) Functional analysis of sterol carrier protein-2 (SCP2) in SCP2 knockout mouse. In: Chang TY, Freeman DA (eds) Intracellular cholesterol trafficking. Kluwer Academic Publishers, Boston, pp 233–252

    Google Scholar 

  29. Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz KWA, Wanders RJA, Maeda N, Assmann G (1998) Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 12:1189–1201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fuchs M, Hafer A, Muench C, Kannenberg F, Teichmann S, Scheibner J, Stange EF, Seedorf U (2001) Disruption of the sterol carrier protein 2 gene in mice impairs biliary lipid and hepatic cholesterol metabolism. J Biol Chem 276:48058–48065

    Article  CAS  PubMed  Google Scholar 

  31. Milligan S, Martin GG, Landrock D, McIntosh AL, Mackie JT, Schroeder F, Kier AB (2017) Impact of dietary phytol on lipid metabolism in SCP2/SCPx/L-FABP null mice. Biochim Biophys Acta Mol Cell Biol Lipids 1862:291–304

    Article  CAS  Google Scholar 

  32. Storey SM, Atshaves BP, McIntosh AL, Landrock KK, Martin GG, Huang H, Johnson JD, Macfarlane RD, Kier AB, Schroeder F (2010) Effect of sterol carrier protein-2 gene ablation on HDL-mediated cholesterol efflux from primary cultured mouse hepatocytes. Am J Physiol 299:244–254

    Google Scholar 

  33. Goto T, Takahashi N, Kato S, Egawa K, Ebisu S, Moriyama T, Fushiki T, Kawada T (2005) Phytol directly activates peroxisome proliferator activated receptor-a (PPARa) and regulates gene expression involved in lipid metabolism in PPARa-expressing HepG2 hepatocytes. Biochem Biophys Res Commun 337:440–445

    Article  CAS  PubMed  Google Scholar 

  34. Kitareewan S, Burka LT, Tomer KB, Parker CE, Deterding LJ, Stevens RD, Forman BM, Mais DE, Heyman RA, McMorris T, Weinberger C (1996) Phytol metabolites are circulating dietary factors that activate the nuclear receptor R × R. Mol Biol Cell 7:1153–1166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ellinghaus P, Wolfrum C, Assmann G, Spener F, Seedorf U (1999) Phytanic acid activates the peroxisome proliferator-activated receptor alpha (PPARalpha) in sterol carrier protein-2-/sterol carrier protein x-deficient mice. J Biol Chem 274:2766–2772

    Article  CAS  PubMed  Google Scholar 

  36. Hanhoff T, Benjamin S, Borchers T, Spener F (2005) Branched-chain fatty acids as activators of peroxisome proliferators. Eur J Lipid Sci Technol 107:716–729

    Article  CAS  Google Scholar 

  37. Hanhoff T, Wolfrum C, Ellinghaus P, Seedorf U, Spener F (2001) Pristanic acid is activator of PPARalpha. Eur J Lipid Sci 103:75–80

    Article  CAS  Google Scholar 

  38. Thigpen JE, Setchell KD, Ahlmark KB, Kocklear J, Spahr T, Caviness GF, Goelz MF, Haseman JK, Newbold RR, Forsythe DB (1999) Phytoestrogen content of purified, open- and closed-formula laboratory animal diets. Lab Sci 49:530–536

    CAS  Google Scholar 

  39. Thigpen JE, Setchell KD, Goelz MF, Forsythe DB (1999) The phytoestrogen content of rodent diets. Envron Health Perspect 107:A182–A183

    Article  CAS  Google Scholar 

  40. Atshaves BP, McIntosh AL, Kier AB, Schroeder F (2010) High dietary fat exacerbates weight gain and obesity in female liver fatty acid binding protein gene ablated mice. Lipids 45:97–110

    Article  CAS  PubMed  Google Scholar 

  41. Nagy TR, Clair A-L (2000) Precision and accuracy of dual-energy X-ray absorptiometry for in vivo body composition in mice. Obes Res 8:392–398

    Article  CAS  PubMed  Google Scholar 

  42. Martin GG, Danneberg H, Kumar LS, Atshaves BP, Erol E, Bader M, Schroeder F, Binas B (2003) Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid binding protein (L-FABP) gene. J Biol Chem 278:21429–21438

    Article  CAS  PubMed  Google Scholar 

  43. Atshaves BP, Petrescu A, Starodub O, Roths J, Kier AB, Schroeder F (1999) Expression and intracellular processing of the 58 kDa sterol carrier protein 2/3-oxoacyl-CoA thiolase in transfected mouse L-cell fibroblasts. J Lipid Res 40:610–622

    CAS  PubMed  Google Scholar 

  44. Martin G, Chung S, Landrock D, Landrock KK, Huang H, Dangott LJ, Peng X, Kaczocha M, Seeger DR, Murphy EJ, Golovko MY, Kier AB, Schroeder F (2016) FABP1 gene ablation impacts brain endocannabinoid system in male mice. J Neurochem 138:407–422

    Article  CAS  PubMed  Google Scholar 

  45. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−DDCT method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  46. Jolly CA, Wilton DA, Schroeder F (2000) Microsomal fatty acyl CoA transacylation and hydrolysis: fatty acyl CoA species dependent modulation by liver fatty acyl CoA binding proteins. Biochim Biophys Acta 1483:185–197

    Article  CAS  PubMed  Google Scholar 

  47. Starodub O, Jolly CA, Atshaves BP, Roths JB, Murphy EJ, Kier AB, Schroeder F (2000) Sterol carrier protein-2 immunolocalization in endoplasmic reticulum and stimulation of phospholipid formation. Am J Physiol 279:C1259–C1269

    CAS  Google Scholar 

  48. Jefferson JR, Slotte JP, Nemecz G, Pastuszyn A, Scallen TJ, Schroeder F (1991) Intracellular sterol distribution in transfected mouse L-cell fibroblasts expressing rat liver fatty acid binding protein. J Biol Chem 266:5486–5496

    CAS  PubMed  Google Scholar 

  49. Chao H, Zhou M, McIntosh A, Schroeder F, Kier AB (2003) Acyl CoA binding protein and cholesterol differentially alter fatty acyl CoA utilization by microsomal acyl CoA: cholesterol transferase. J Lipid Res 44:72–83

    Article  CAS  PubMed  Google Scholar 

  50. Li T, Chiang JYL (2009) Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res 2009 (article ID 501739-15)

  51. Repa JJ, Mangelsdorf DJ (2000) The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 16:459–481

    Article  CAS  PubMed  Google Scholar 

  52. Trauner M, Boyer JL (2003) Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 83:633–671

    Article  CAS  PubMed  Google Scholar 

  53. Murphy EJ, Prows DR, Jefferson JR, Schroeder F (1996) Liver fatty acid binding protein expression in transfected fibroblasts stimulates fatty acid uptake and metabolism. Biochim Biophys Acta 1301:191–198

    Article  PubMed  Google Scholar 

  54. Murphy EJ (1998) L-FABP and I-FABP expression increase NBD-stearate uptake and cytoplasmic diffusion in L-cells. Am J Physiol 275:G244–G249

    CAS  PubMed  Google Scholar 

  55. McArthur MJ, Atshaves BP, Frolov A, Foxworth WD, Kier AB, Schroeder F (1999) Cellular uptake and intracellular trafficking of long chain fatty acids. J Lipid Res 40:1371–1383

    CAS  PubMed  Google Scholar 

  56. Storey SM, McIntosh AL, Huang H, Martin GG, Landrock KK, Landrock D, Payne HR, Kier AB, Schroeder F (2012) Intracellular cholesterol binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes. Am J Physiol Gastrointest Liver Phys 302:G824–G839

    Article  CAS  Google Scholar 

  57. Storey SM, McIntosh AL, Huang H, Martin GG, Landrock KK, Landrock D, Payne HR, Kier AB, Schroeder F (2012) Loss of intracellular lipid binding proteins differentially impacts saturated fatty acid uptake and nuclear targeting in mouse hepatocytes. Am J Physiol Gastrointest Liver Phys 303:G837–G850

    Article  CAS  Google Scholar 

  58. Martin GG, Atshaves BP, Landrock KK, Landrock D, Storey SM, Howles PN, Kier AB, Schroeder F (2014) Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion. Am J Physiol Gastrointest Liver Phys 307:G1130–G1143

    Article  CAS  Google Scholar 

  59. Martin GG, Landrock D, Landrock KK, Howles PN, Atshaves BP, Kier AB, Schroeder F (2015) Relative contributions of L-FABP, SCP-2/SCP-x, or both to hepatic biliary phenotype of female mice. Arch Biochem Biophys 588:25–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Martin GG, Atshaves BP, Landrock KK, Landrock D, Schroeder F, Kier AB (2015) Loss of L-FABP, SCP-2/SCP-x, or both induces hepatic lipid accumulation in female mice. Arch Biochem Biophys 580:41–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Storey SM, Huang H, McIntosh AL, Martin GG, Kier AB, Schroeder F (2017) Impact of Fabp1/SCP-2/SCP-x gene ablation (TKO) on hepatic phytol metabolism. J Lipid Res Revis Pending

  62. Yoon M (2009) The role of PPARa in lipid metabolism and obesity: focusing on the effects of estrogen on PPARa actions. Pharm Res 60:151–159

    Article  CAS  Google Scholar 

  63. Burri L, Thoresen GH, Berge RK (2010) The role of PPARα activation in liver and muscle. PPAR Res. doi:10.1155/2010/542359

    PubMed  PubMed Central  Google Scholar 

  64. Huang H, Starodub O, McIntosh A, Kier AB, Schroeder F (2002) Liver fatty acid binding protein targets fatty acids to the nucleus: real-time confocal and multiphoton fluorescence imaging in living cells. J Biol Chem 277:29139–29151

    Article  CAS  PubMed  Google Scholar 

  65. Huang H, Starodub O, McIntosh A, Atshaves BP, Woldegiorgis G, Kier AB, Schroeder F (2004) Liver fatty acid binding protein colocalizes with peroxisome proliferator receptor alpha and enhances ligand distribution to nuclei of living cells. Biochemistry 43:2484–2500

    Article  CAS  PubMed  Google Scholar 

  66. McIntosh AL, Huang H, Atshaves BP, Wellburg E, Kuklev DV, Smith WL, Kier AB, Schroeder F (2010) Fluorescent n-3 and n-6 very long chain polyunsaturated fatty acids: three photon imaging and metabolism in living cells overexpressing liver fatty acid binding protein. J Biol Chem 285:18693–18708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. McIntosh AL, Atshaves BP, Hostetler HA, Huang H, Davis J, Lyuksyutova OI, Landrock D, Kier AB, Schroeder F (2009) Liver type fatty acid binding protein (L-FABP) gene ablation reduces nuclear ligand distribution and peroxisome proliferator activated receptor-alpha activity in cultured primary hepatocytes. Arch Biochem Biophys 485:160–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Petrescu AD, McIntosh AL, Storey SM, Huang H, Martin GG, Landrock D, Kier AB, Schroeder F (2013) High glucose potentiates liver fatty acid binding protein (L-FABP) mediated fibrate induction of PPARa in mouse hepatocytes. Biochim Biophys Acta 1831:1412–1425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Petrescu AD, Huang H, Martin GG, McIntosh AL, Storey SM, Landrock D, Kier AB, Schroeder F (2013) Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARa regulated b-oxidative enzymes. Am J Physiol Gastrointest Liver Phys 304:G241–G256

    Article  CAS  Google Scholar 

  70. Hostetler HA, McIntosh AL, Atshaves BP, Storey SM, Payne HR, Kier AB, Schroeder F (2009) Liver type fatty acid binding protein (L-FABP) interacts with peroxisome proliferator activated receptor-a in cultured primary hepatocytes. J Lipid Res 50:1663–1675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hostetler HA, Huang H, Kier AB, Schroeder F (2008) Glucose directly links to lipid metabolism through high-affinity interaction with peroxisome proliferator activated receptor-alpha. J Biol Chem 283:2246–2254

    Article  CAS  PubMed  Google Scholar 

  72. Schroeder F, Petrescu AD, Huang H, Atshaves BP, McIntosh AL, Martin GG, Hostetler HA, Vespa A, Landrock K, Landrock D, Payne HR, Kier AB (2008) Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription. Lipids 43:1–17

    Article  CAS  PubMed  Google Scholar 

  73. Hughes MLR, Liu B, Halls ML, Wagstaff KM, Patil R, Velkov T, Jans DA, Bunnett NW, Scanlon MJ, Porter CJH (2015) FABPs 1 and 2 differentially modulate the activation of PPARa in a ligand selective manner. J Biol Chem 290:13895–13906. doi:10.1074/jbc.M114.605998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Velkov T (2013) Interactions between human liver fatty acid binding protein and peroxisome proliferator activated receptor drugs. PPAR Res 2013:1–14

    Article  Google Scholar 

  75. Huang H, McIntosh AL, Martin GG, Landrock K, Landrock D, Gupta S, Atshaves BP, Kier AB, Schroeder F (2014) Structural and functional interaction of fatty acids with human liver fatty acid binding protein (L-FABP) T94A variant. FEBS J 281:2266–2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Martin GG, McIntosh AL, Huang H, Gupta S, Atshaves BP, Kier AB, Schroeder F (2013) Human liver fatty acid binding protein (L-FABP) T94A variant alters structure, stability, and interaction with fibrates. Biochemistry 52:9347–9357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. McIntosh AL, Huang H, Storey SM, Landrock K, Landrock D, Petrescu AD, Gupta S, Atshaves BP, Kier AB, Schroeder F (2014) Human FABP1 T94A variant impacts fatty acid metabolism and PPARa activation in cultured human female hepatocytes. Am J Physiol Gastrointest Liver Phys 307:G164–G176

    Article  CAS  Google Scholar 

  78. Sugiyama MG, Agellon LB (2012) Sex differences in lipid metabolism and metabolic disease risk. Biochem Cell Biol 90:124–141

    Article  CAS  PubMed  Google Scholar 

  79. Lorbek G, Perse M, Horvat S, Bjorkhem I, Rozman D (2013) Sex differences in hepatic cholesterol sensing mechanisms in mice. Molecules 18:11067–11085

    Article  CAS  PubMed  Google Scholar 

  80. Rando G, Wahli W (2011) Sex differences in nuclear receptor regulated liver metabolic pathways. Biochim Biophys Acta 1812:964–973

    Article  CAS  PubMed  Google Scholar 

  81. Varlamov O, Bethea CL, Roberts CT (2015) Sex-specific differences in lipid and glucose metabolism. Front Endocrinol 5:1–7

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by US Public Health Service/National Institutes of Health Grants RO1 DK41402 (FS, ABK), R25 OD 016574 (SM, ABK), and NIH T35 OD010991 Veterinary Scholars Program, CVM (SM, ABK).

Author information

Authors and Affiliations

  1. Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, TVMC, College Station, TX, 77843-4467, USA

    Danilo Landrock, Sherrelle Milligan, Kerstin K. Landrock & Ann B. Kier

  2. Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4466, USA

    Gregory G. Martin, Avery L. McIntosh & Friedhelm Schroeder

Authors
  1. Danilo Landrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sherrelle Milligan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregory G. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Avery L. McIntosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kerstin K. Landrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Friedhelm Schroeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ann B. Kier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ann B. Kier.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest, financial, or otherwise.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Landrock, D., Milligan, S., Martin, G.G. et al. Effect of Fabp1/Scp-2/Scp-x Ablation on Whole Body and Hepatic Phenotype of Phytol-Fed Male Mice. Lipids 52, 385–397 (2017). https://doi.org/10.1007/s11745-017-4249-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-017-4249-y

Keywords

Search

Navigation