THE EFFECT OF DIETARY CHOLINE ON LIPID PARTITIONING

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THE EFFECT OF DIETARY CHOLINE ON LIPID PARTITIONING AND PROTECTION FROM METABOLIC SYNDROME Laila

THE EFFECT OF DIETARY CHOLINE ON LIPID PARTITIONING AND PROTECTION FROM METABOLIC SYNDROME Laila Cigana Shenkel, Adrian Taylor and Marica Bakovic Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada

WHOLE BODY CHOLINE UTILIZATION liver Diet bile PC small intestine PC Acetylcholine neurotransmission Betaine

WHOLE BODY CHOLINE UTILIZATION liver Diet bile PC small intestine PC Acetylcholine neurotransmission Betaine and PC synthesis Choline Betaine brain PC lyso-PC+ FA lung SM PC muscle GPC free Choline PC Choline Neuromuscular transmission Betaine lyso-PC Sphingomyelin lyso. PC Sphingomyelin enterocytes SM kidney Betaine synthesis Choline excretion and reabsorption Betaine Choline

Choline prevents weight gain and reduces fat accumulation 2 4 Time (weeks) +c ho

Choline prevents weight gain and reduces fat accumulation 2 4 Time (weeks) +c ho ET ET 0 6 H 50 49 48 47 46 45 44 43 42 49 48. 5 48 47. 5 47 46. 5 46 45. 5 45 H WT KO KO+Cho W T HET/ Knockout Male weight (g) Wild type Weight Change ( AUC) ETKO mice 4 weeks of 2 mg/ml choline in drinking water = 230 -240µg of choline/gr body-weight/day * * * # # # J Nutr Biochem 2015

CHOLINE PREVENTS LIVER STEATOSIS HET + Cho C. * Liver TAG (mg/g) WT A.

CHOLINE PREVENTS LIVER STEATOSIS HET + Cho C. * Liver TAG (mg/g) WT A. WT HET + Cho D. * Plasma TAG (mg/ml B. A. Lipid droplets (fatty liver) B. Collagen deposition (scar tissue) WT HET + Cho

CHOLINE METABOLISM CHOLINE BETAINE BHMT P-choline THF Dimethylglycine 5 -m. THF 5, 10 -m.

CHOLINE METABOLISM CHOLINE BETAINE BHMT P-choline THF Dimethylglycine 5 -m. THF 5, 10 -m. THF ATP ADP CTP PPi CDP-choline DAG Pcyt 1 Homocysteine Methionine SAH SAM PHOSPHATIDYLCHOLINE PEMT DAG + Choline FA Phosphatidylethanolamine (PE) PSS 1 PSS 2 PSD Phosphatidylserine (PS) Lyso. PC + FA TAG

Choline does not modify expression of phospholipid genes Choline transport PC synthesis PC/PS exchange

Choline does not modify expression of phospholipid genes Choline transport PC synthesis PC/PS exchange * # PE/PS exchange PE formation from PS PC formation from PE

CHOLINE IMPROVES LIPID RAFT COMPOSITION Phospholipids: PC/PE * * Sphingomyelin * Cholesterol/Sphingomyelin * #

CHOLINE IMPROVES LIPID RAFT COMPOSITION Phospholipids: PC/PE * * Sphingomyelin * Cholesterol/Sphingomyelin * #

Choline increases membrane PC turnover and reduces TAG (fat) formation from FA A. B.

Choline increases membrane PC turnover and reduces TAG (fat) formation from FA A. B. * C. D. * * *

Choline stimulates TAG and FA degradation and inhibits their formation by lipogenesis TAG degradation

Choline stimulates TAG and FA degradation and inhibits their formation by lipogenesis TAG degradation TAG synthesis *# *# *# * * *# * # *# # * FA synthesis FA oxidation *#

H 3 -NMR PLASMA METABOLOMICS TCA cycle Threonine Gluconeogenesis Lysine Taurine 3 HB Cysteine

H 3 -NMR PLASMA METABOLOMICS TCA cycle Threonine Gluconeogenesis Lysine Taurine 3 HB Cysteine Glutamine Succinate Glucose Homocysteine Serine SAH Glycine Creatine Cystathione Betaine Choline PE BHMT SAM Dimethylglycine Sarcosine Acetate Methionine β-Oxidation Glycerol Lipolysis PNMT PC Epinephrine

CONCLUSION Choline supplementation reduces hypertriglyceridemia, liver steatosis and obesity The reduction mechanism includes stimulation

CONCLUSION Choline supplementation reduces hypertriglyceridemia, liver steatosis and obesity The reduction mechanism includes stimulation of lipolysis and fatty acid oxidation Choline supplementation improves membrane lipid rafts-sphingomyelin and cholesterol ratio The incorporation into one-carbon cycle is the main metabolic change associated with choline supplementation