, Volume 51, Issue 6, pp 655–676 | Cite as

Fatty Acid Binding Protein-1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias

  • Friedhelm SchroederEmail author
  • Avery L. McIntosh
  • Gregory G. Martin
  • Huan Huang
  • Danilo Landrock
  • Sarah Chung
  • Kerstin K. Landrock
  • Lawrence J. Dangott
  • Shengrong Li
  • Martin Kaczocha
  • Eric J. Murphy
  • Barbara P. Atshaves
  • Ann B. Kier


The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine, and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear—especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human single nucleotide polymorphism (SNP) (26–38 % minor allele frequency and 8.3 ± 1.9 % homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant’s impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system in hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.


Liver Fatty acid binding protein (FABP1) Triglyceride 



Acetyl-CoA carboxylase


Acyl-CoA oxidase 1, palmitoyl


N-Arachidonoylethanolamide (anandamide)






C20:4n-6 arachidonic acid


Cannabinoid receptor-1


Cannabinoid receptor-2


Carnitine palmitoyl transferase IA, liver


Carnitine palmitoyl-CoA transferase II


Diacylglycerol lipase-α


Diacylglycerol lipase-β


11-(Dansylamino)undecanoic acid


Diacylglycerol O-acyltransferase 2


C22:6n-3 docosahexaenoic acid


Arachidonic acid-containing endocannabinoids (AEA, 2-AG)


Non-ARA-containing N-acylethanolamides and 2-monoacylglycerols


C20:5n-3 eicosapentaenoic acid


Fatty acid amide hydrolase


Liver fatty acid binding protein or FABP1


Human FABP1 T94A variant


Wild-type (WT) human FABP1


Heart fatty acid binding protein


Adipocyte fatty acid binding protein


Epidermal fatty acid binding protein


Brain fatty acid binding protein


FABP1 gene ablated mouse on C57BL/6NCr background


Fatty acid synthase




Glycerol-3-phosphate acyltransferase, mitochondrial


G protein-coupled receptors other than CB1/CB2


G protein-coupled receptor 119


High-density lipoprotein


Hepatocyte nuclear factor-4α


Long chain fatty acids, unesterified


Long chain fatty acid-CoA thioester


Low-density lipoprotein


Low-density lipoprotein-C


Low-density lipoprotein (LDL) receptor


Lipoprotein lipase


Laser scanning confocal microscopy


Monoacylglycerol lipase


Microsomal triglyceride transfer protein


N-Acylethanolamide acid amide hydrolase


Non-alcohol fatty liver disease


N-Acyl phosphatidylethanolamine phospholipase D


NBD-N-arachidonoylethanolamide or [20-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino] arachidonoylethanolamide


NBD-2-arachidonoylglycerol or 2-[20-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino] arachidonoyl glycerol


NBD-arachidonic acid or [20-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]arachidonic acid



NBD-stearic acid

[12-N-Methyl-(7-nitrobenz-2-oxa-1,3-diazo)aminostearic acid]













PPARα, β/δ, or γ

Peroxisome proliferator activated receptor alpha, beta/delta, or gamma


Stearoyl CoA desaturase


Sterol carrier protein-2


Sterol carrier protein-X


Single nucleotide polymorphism


Scavenger receptor class B member 1


Sterol regulatory element binding protein-1c




Very-low-density lipoprotein


Wild-type C57BL/6NCr mouse



This work was supported in part by the US Public Health Service/National Institutes of Health Grant R25 OD016574 (A.B.K.), Merial Veterinary Scholars Program, CVM (A.B.K.), and DA035923 and DA032232 (M.K.).


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Copyright information

© AOCS 2016

Authors and Affiliations

  • Friedhelm Schroeder
    • 1
    Email author
  • Avery L. McIntosh
    • 1
  • Gregory G. Martin
    • 1
  • Huan Huang
    • 1
  • Danilo Landrock
    • 2
  • Sarah Chung
    • 2
  • Kerstin K. Landrock
    • 2
  • Lawrence J. Dangott
    • 3
  • Shengrong Li
    • 4
  • Martin Kaczocha
    • 5
  • Eric J. Murphy
    • 6
  • Barbara P. Atshaves
    • 7
  • Ann B. Kier
    • 2
  1. 1.Department of Physiology and PharmacologyTexas A&M UniversityCollege StationUSA
  2. 2.Department of PathobiologyTexas A&M UniversityCollege StationUSA
  3. 3.Department of Biochemistry and BiophysicsTexas A&M UniversityCollege StationUSA
  4. 4.Avanti Polar LipidsAlabasterUSA
  5. 5.Department of AnesthesiologyStony Brook UniversityStony BrookUSA
  6. 6.Department of Pharmacology, Physiology, and Therapeutics and ChemistryUniversity of North DakotaGrand ForksUSA
  7. 7.Department of Biochemistry and Molecular BiologyMichigan State UniversityEast LansingUSA

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