Diet alters fatty acid composition in C.elegans

Kaja Reisner

CATEGORIES OF LIPIDS• Fatty acyls • Glycerolipids • Glycerophospholipids • Sphingolipids • Sterol lipids • Prenol lipids • Saccharolipids • Polyketides

FUNCTIONS OF LIPIDS

Color scheme: PO4 = green; N(CH3)3 = violet; water = blue; terminal CH3 = yellow; O = red; glycol C = brown; C chain = grey

1. Membranes- phospholipids, sphingomyelin, sterols

FUNCTIONS OF LIPIDS

2. Energy storage and metabolism – glycerolipids (mainly triacylglycerols)

FUNCTIONS OF LIPIDS3. Signaling

- sphingolipids, prostaglandins, steroid hormones, oxysterols, DAG, PIPs

FATTY ACIDS

POLYUNSATURATED FATTTY ACIDSessential fatty acids

(EFA) :

linoleic acid C18:2n-6 (omega 6)

α-linolenic acid C18:3n-3 (omega 3)”optimal” ratio is 2:1 to 3:1, due to competition with delta-6- desaturase

PUFA metabolism

cis AND trans

Trans fatty acids (TFA)

Dyerberg et al., 2006

Trans fatty acids – scary facts

Nematode C. elegans

• ChromosomesChromosomes 5 + 1 5 + 1 22 + 222 + 2• Genome SizeGenome Size 97 million 97 million 3000 million 3000 million• Encoded ProteinsEncoded Proteins 19,099 19,099 ~30,000~30,000• Life SpanLife Span 0.06 years 0.06 years ~80 years ~80 years• SexesSexes male, herm. male, herm. male, female male, female• NeuronsNeurons 381, 302 381, 302 100,000,000,000 100,000,000,000• Synaptic connectionsSynaptic connections 5,000 5,000

100,000,000,000,000100,000,000,000,000• Somatic cellsSomatic cells 1031, 959 1031, 959 ??? ???• Body sizeBody size 1 mm 1 mm ~170 cm ~170 cm• Body weightBody weight 5 5 gg ~75 kg ~75 kg• FoodFood E.coli E.coli Omnivore Omnivore

omega-3

omega-6

Δ9Δ12fat-2

Δ15fat-1

Δ6fat-3 elongase

Δ5fat-4

WORM PUFA METABOLISM

Δ6fat-3 elongase

Δ5fat-4

Δ15fat-1 Δ15

fat-1

Δ15fat-1

oleicLA

ALA stearidonic

GLA

fat-3

o dumpy body shape (cuticle defects)o slowed developmento abnormalities in egg-layingo neuronal impairment o behavioral defects

etc.

FAT DIET : OLEIC AND ELAIDIC ACID• Strains: N2 and fat-3 (Δ-6 desaturase)• Assay:

brood sizefatty acid analysis (GC-MS)

• Plates:control (NGM)cis-oleic acid (triglyceride)elaidic (trans-oleic) acid (triglyceride)

FAT DIET DOES NOT SIGNIFICANTLY AFFECT BROOD SIZE IN N2 WORMS

N2 first generation

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350

control cis trans

N2 third generation

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control cis trans

FAT DIET REDUCES BROOD SIZE IN fat-3 WORMS

fat- 3 fi rst generation

0

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100

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control cis trans

fat- 3 third generation

0

50

100

150

200

250

control cis trans

*****

p = 0.003 p = 0.016 p = 2.82E-07

Fat diet has no effect on life span of N2 worms

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

N2 NGM

N2 cis

N2 trans

trans-fat kills fat-3 worms

0

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1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

fat-3 NGM

fat-3 cis

fat-3 trans

whereas cis-fat has no effect

TRANS-FATS AND HUMAN PUFA DEFICIENCY – fat-3 WORMS AS A MODEL?

• PUFA biosynthesis is deficient or inhibited in diabetes, obesity, older people, and in the presence of insulin, coffee, alcohol, or trans fatty acids

• There are alltogether 45 SNPs in human delta-6-desaturases (FADS1, FADS2 and FADS3)

- are individuals with reduced fatty acid desaturase expression more vulnerable to trans-fat diet?

THANK YOU !UNIVERSITY OF KUOPIO

A.I. Virtanen Institute

Dept. of Neurobiology

Research group: Functional Genomics and Bioinformatics

Garry Wong

James Callaway

Tanel Jantson

Marko Lehtonen (Dept. of Pharmaceutical Chemistry)

Ye have made your way from the worm to man, and much within

you is still worm. (Friedrich

Nietzsche)