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Lecture 13 Dietary Fat Dietary Fat • 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 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 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 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 lipase FAT Chol Bile salts Digestion - Pancreatic Lipase 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 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) 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/ Lipoproteins • • • • The phospholipid shell can be up to 1 mm 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