MOREonLIPIDS….
KaraL.Calkins,MD,MS
UniversityofCalifornia,LosAngeles
Ma@elChildren’sHospital
DepartmentofPediatrics
DivisionofNeonatology,UCLA
NIH/NCATSKL2TR000122
ObjecKves
•  DifferencesIVlipidformulaKons
•  WhatmakesIVlipidshepatotoxic?
ParenteralNutriKon
Sugar
Protein
FAT
Lipids
• 
• 
• 
• 
Calories
EssenKalFa@yAcids
CellSignaling
ProducKonofavarietyofhormone-like
substances
–  Thrombaxanes,Leukotrienes,Prostagladins
•  CogniKveandVisualDevelopment
IntesKnalFailureAssociatedLiver
Disease
IVFa@yAcids
1960s:
Intralipid™
SoybeanOil
OnlyFDAApprovedforChildren
1980s:
Lipofundin™
SoybeanOil/
CoconutOil
2000s:
Omegaven™
FishOil
2000s:
SMOF™
CombinaKon
Coconutoil:MCT
OliveOil:Omega-9FaByAcids
2013:
Clinoleic™/Clinolipid™
SoybeanOil/OliveOil
FISHOILSoybeanOil
MedianKmefordirbili<2:9.4weeks
SurvivorsreceivingFO:3.8Kmesmorelikelytoreverse
cholestasis
Gura,Pediatr,2008
GeometricMeanBilirubin(mg/dL)
16
FishOilDecreasedTotalandDirect
Bilirubin
14
12
10
8
#
6
4
*
2
#
0
SOTB
FODB
SODB
FOTB
SOTB
FODB
SODB
FOTB
0
7.0
6.1
4.1
10.2
4
8.7
6.6
5.3
11.7
8
10.2
2.9
6.6
5.3
*
12
11.9
1.3
6.6
2.7
*
*
*
*
*
20
*
24
16
11.0
0.7
6.3
1.5
12.3
0.3
7.0
0.8
13.7
0.2
7.4
0.6
n,FO10988865
n,FO2020181816115
Weeks
Figure1.Geometricmeantotalbilirubin(TB)anddirectbilirubin(DB)withthestandarderrorofthe
meanforthefishoilandsoybeanoilgroup.*p<0.001.#p<0.05.
CalkinsetalJPEN2013
FishOilBiochemicallyReversesIFALD
%ofSubjectsWhoseCholestasis
Resolved
100
80
p-value<0.0001
60
FO
SO
40
20
0
0
3
6
9
12
15
18
Weeks
CalkinsetalJPEN2013
IntralipidDose:0.5-3g/kg/d
OmegavenDose:1g/kg/d
SMOF:2-3g/kg/d
Calkinsetal,ClinicsofPerinatology2014
FATTYACIDS
Omega-6
Omega-3
Stearic,
4%
Intralipid
PalmiKc,
20%
Linoleic,
51%
Oleic,26%
αlinolenic,
9%
Stearic
2%
PalmiKc
8%
DHA
29%
Oleic
25%
α-linolenic
2%
EPA
26%
Omegaven
ARA
3%
Linoleic
5%
Decreaseinω-6andIncreaseinω-3
%ofRBC
16
12
*
8
*
Linoleic
ARA
*
*
4
*
*
0
0
4
*
12
%ofRBC
8 12 16
StudyWeek
8
*
4
*
*
20
24
*
Linolenic
EPA
*
DHA
0
0
4
8
12 16 20 24
StudyWeek
Dataispresentedasamean(±SEM),each\mepointis
comparedtobaseline.n=14,*p<0.01
†
Baseline
2 wk
3 mo
6 mo
pg/mL
80
*
40
pg/mL
30
4
†
2
0
IL-8
40
*
Baseline
2 wk
3 mo
6 mo
*
0
IL-6
pg/mL
FishoilDecreasesInflammaKon
Baseline
2 wk
3 mo
6 mo
IL-10
* †
IL-β
*
20
10
0
IFN-γ
TNF-α
Dataispresentedasamean(±SEM),each\mepointiscomparedtobaseline.n=14,*p<0.01,†p<0.05
PHYTOSTEROLS
Phytosterols
Phytosterols
Phytosterols
Liver Function
Platelets
Clayton, PT. Gastroenterol, 1993
DecreaseinPhytosterols
Baseline
2wk
3mo
6mo
mg/dL
16
12
*
8
4
0
* *
Campesterol
*
*
* *
SKgmasterol
*
Sitosterol
Dataispresentedasamean(±SEM),each\mepointiscomparedto
baseline.n=14,*p<0.01
Phytosterols
+
TNF-α/IL-6
ElKasmi.SciTranslMed2013
--
- LXR
- FXR
ABCG5/
--
8
--
--
Cholesterolbileacids-- BSEP
Cholesterol7α-hydroxylase
NTCP
LiverCell
--
InflammaKon
Omega-3Fa@yAcids?Phytosterols?
VitaminE?
InfluencedbyDoseandComposiKonoftheIntravenousFa@y
AcidEmulsion
Sepsis
Phytosterols
An\oxidants
InflammaKon
BileAcid/Bilirubin
Transport
Omega-6:
Omega-3RaKo
Lipid
Accumula\on
CHOLESTASISS
STEATOSIS
FIBROSIS
CIRRHOSIS
Calkinsetal,
ClinicsofPerinatology2014
Conclusion
•  IVLipidsareimportant
•  ResearchonIVlipidshasprovideduswitha
be@erunderstandingofIFALD
•  NewformulaKonsaresKllbeinginvesKgated
forclinicaluse