1. Lecture 13 Dietary Fat

2. Lipogenesis is not very active in people on a Western diet –Lipogenic enzyme expression is down-regulated by fat consumption –Most of our fat comes from the diet ~100g/day –Most fat in white adipose tissue will have come from dietary fat and not de novo lipogenesis Fat is hydrophobic –Problems for digestion and transport –Digestive enzymes need fat to be in an emulsion –Fat needs to be carried around the bloodstream within lipoproteins

3. Formation of Emulsions Needs molecules which have both hydrophilic and hydrophobic characteristics –amphiphilic –amphipathic Phospolipids that comprise cell membranes are ampiphatic –As is the phosphatidic acid and lysolecithin that you use in salad dressing Amphiphilic molecules act as detergents which emulsify fat into tiny ‘particles’ –micelles

4. Bilayers and Micelles In both structures, polar heads are facing the aqueous environment while the hydrophobic tails are buried in the core Micelles can also be formed using bile salts

5. Fat Digestion Fat is trapped in the core of micelles formed with bile salts Churning of dietary fat with bile salts in the intestine –Chyme –Emulsion –Easy for lipase to interact with Pancreatic Lipase –Hydrolyses fat into FA and glycerol –Plus mixture of mono- and di-acyl glycerols FAT Chol lipase Bile salts

6. Digestion - Pancreatic Lipase

7. Bile Salts Produced in the liver Made from cholesterol –Cholesterol itself it not amphiphilic enough to be a detergent  needs modification by addition of polar groups Stored in the gall bladder Reabsorbed and taken back to the liver –Hepatic portal vein

8. Bile Salts Polar groups are added to cholesterol to make it more amphiphilic The only way to get rid of cholesterol is to make them into bile salts (chol cannot be oxidised)

9. Undigested Fat If gall bladder is blocked by gall stones, no bile salts can be secreted into the small intestine  no fat digestion –Less calorie intake –But more oily stools Inhibitors of fat digestion as weight-loss drugs –Orlistat (brand name Xenical) is an inhibitor of lipase Listed side effects include –oily spotting; –oily or fatty stools; –orange or brown colored oil in your stool; –gas with discharge, an oily discharge; –an urgent need to go to the bathroom; –an inability to control bowel movements, –an increased number of bowel movements. Olestra (Olean) is a fat substitute –FA attached to sucrose –Not attacked by lipases Olestra will passes through gut undigested –Strips fat soluble vitamins D, E, K need to be added as supplements –See anti-Olestra sites at www.cspinet.org/olestra/

10. Lipoproteins The phospholipid shell can be up to 1  m in diameter Apoproteins –Enzymes –Structural –Docking Different types of lipoproteins characterised by size and by types of apoproteins First lipoproteins made by intestinal cells –Chylomicrons –Enter lymphatic system