diet alters fatty acid composition in c.elegans
DESCRIPTION
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. Membranes - phospholipids, sphingomyelin, sterols. - PowerPoint PPT PresentationTRANSCRIPT
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
0
50
100
150
200
250
300
350
control cis trans
N2 third generation
0
50
100
150
200
250
300
350
control cis trans
FAT DIET REDUCES BROOD SIZE IN fat-3 WORMS
fat- 3 fi rst generation
0
50
100
150
200
250
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
0
10
20
30
40
50
60
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
10
20
30
40
50
60
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)