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The Impact of Early Life Over- and Undernutrition on Fatty Acid Composition in Brain Lipids and their Association to Leptin-Related Gene Expression

Chris

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Hypothesis:Metabolic programming in early life causes changes in the brain lipid composition which might cause impaired leptin signalling.

Nutrition-induced programming of the brain lipid composition Appetite dysregulation

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Experimental setup - Sheep study3x2 factorial design feeding experiment

• Membrane lipid derived fatty acids in Cortex• mRNA expression of key genes involved in leptin signalling in hypothalamusCh

ristin

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p - D

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Biol

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Tec

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of D

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Kgs

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50% of requirements

150% of requirements

100% of requirements

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HCHF n=16 Conv n=190

1

2

3

4

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Relative C22:4n-6

Post-partum nutrition

C2

2:4

n-6

[%

]

p=0.0021

**

Results – Principal Component AnalysesImpact of early life overfeeding on brain cortex fatty acid composition

HCHF n=16 Conv n=19-4

-2

0

2

4

6

Principal Component Analysis

Post-partum nutrition

PC

#2

sc

ore

va

lue

[a

u]

p=0.0128

*

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Box: 25-75 PercentileWhiskers: Min-Max

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Results – Correlation analysesCortex fatty acids and Leptin signaling

0.0 0.1 0.2 0.3 0.4 0.50.0

0.5

1.0

1.5

C22:5n-6 vs. STAT3

Relative C22:5n-6 [%] n=34

ST

AT

3 e

xp

res

sio

n p=0.0252

*

14 16 18 20 22 240.0

0.5

1.0

1.5

C18:0 vs. STAT3

Relative C18:0 [%] n=34S

TA

T3

ex

pre

ss

ion p=0.005

**

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Conclusion• Post-partum overfeeding influences the cortex FA composition.

• Nutrition induced changes in the brain FA composition are detectable even into adulthood

• Pre-partum over- or underfeeding does not have any detectable effect on the cortex FA composition

• There is an association between percentages of certain FAs in cortex and expression of especially STAT3 in the hypothalamus

-4 -2 0 2 4 60.0

0.5

1.0

1.5

PC#2 vs. STAT3

PC#2 score value [au] n=34

ST

AT

3 e

xp

res

sio

n p=0.0389

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Thank you for listening!

Lærke Johnsen – Department of Veterinary Clinical and Animal Science, University of Copenhagen, Frederiksberg, Denmark

Mette Olaf Nielsen – Department of Veterinary Clinical and Animal Science, University of Copenhagen, Frederiksberg, Denmark

Lars I. Hellgren – Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark

Acknowledgements

Referenceshttp://www.thebabycorner.com/pregnancy-calendar/week-36/http://keckmedicine.adam.com/content.aspx?productId=117&pid=1&gid=003272http://medillsb.com/ArtistPortfolioLarge.aspx?IID=146889&AID=4962

Chris

tine

Hee

rup

- Dep

artm

ent o

f Sys

tem

s Bi

olog

y, T

echn

ical

Uni

vers

ity o

f Den

mar

k, K

gs. L

yngb

y, D

enm

ark,