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Diet alters fatty acid composition in C.elegans

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.

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Diet alters fatty acid composition in C.elegans

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  1. Diet alters fatty acid composition in C.elegans Kaja Reisner

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

  3. FUNCTIONS OF LIPIDS • Membranes • - phospholipids, sphingomyelin, sterols Color scheme: PO4 = green; N(CH3)3 = violet; water = blue; terminal CH3 = yellow; O = red; glycol C = brown; Cchain = grey

  4. FUNCTIONS OF LIPIDS 2. Energy storage and metabolism – glycerolipids (mainly triacylglycerols)

  5. FUNCTIONS OF LIPIDS 3. Signaling - sphingolipids, prostaglandins, steroid hormones, oxysterols, DAG, PIPs

  6. FATTY ACIDS

  7. POLYUNSATURATED FATTTY ACIDS essential 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

  8. PUFA metabolism

  9. cis AND trans

  10. Trans fatty acids (TFA) Dyerberg et al., 2006

  11. Trans fatty acids – scary facts

  12. Nematode C. elegans

  13. Chromosomes 5 + 1 22 + 2 • Genome Size 97 million 3000 million • Encoded Proteins 19,099 ~30,000 • Life Span 0.06 years ~80 years • Sexes male, herm. male, female • Neurons 381, 302 100,000,000,000 • Synaptic connections 5,000 100,000,000,000,000 • Somatic cells 1031, 959 ??? • Body size 1 mm ~170 cm • Body weight 5 g ~75 kg • Food E.coli Omnivore

  14. WORM PUFA METABOLISM Δ6 fat-3 elongase Δ5 fat-4 Δ15 fat-1 ALA stearidonic Δ12 fat-2 Δ9 Δ15 fat-1 Δ15 fat-1 Δ15 fat-1 LA oleic Δ6 fat-3 elongase Δ5 fat-4 GLA omega-3 omega-6

  15. fat-3 • dumpy body shape (cuticle defects) • slowed development • abnormalities in egg-laying • neuronal impairment • behavioral defects • etc.

  16. FAT DIET : OLEIC AND ELAIDIC ACID • Strains: N2 and fat-3 (Δ-6 desaturase) • Assay: • brood size • fatty acid analysis (GC-MS) • Plates: • control (NGM) • cis-oleic acid (triglyceride) • elaidic (trans-oleic) acid (triglyceride)

  17. FAT DIET DOES NOT SIGNIFICANTLY AFFECT BROOD SIZE IN N2 WORMS

  18. * ** ** p = 0.016 p = 0.003 FAT DIET REDUCES BROOD SIZE IN fat-3 WORMS p = 2.82E-07

  19. Fat diet has no effect on life span of N2 worms

  20. trans-fat kills fat-3 worms whereas cis-fat has no effect

  21. 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 SNPsin human delta-6-desaturases (FADS1, FADS2 and FADS3) - are individuals with reduced fatty acid desaturase expression more vulnerable to trans-fat diet?

  22. 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)

  23. Ye have made your way from the worm to man, and much within you is still worm. (Friedrich Nietzsche)

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