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AHS13 Victoria Prince Fatty Liver -- Is It the Fat's Fault?


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AHS13 Victoria Prince Fatty Liver -- Is It the Fat's Fault?

  1. 1. Fatty Liver: Is it the (dietary) fats’ fault? Victoria Prince PhD, MSIV
  2. 2. Fatty Liver Disease “2 hit” theory
  3. 3. Fatty Liver disease Control Alcohol-fed
  4. 4. How does the fat get there? Major Factors •Alcohol •Sugars •Fats Synthesis •Nutrient Deficiency Export •Vitamin D (?) Metabolism •Microbiota •Inflammation Cohen et al 2011
  5. 5. Models of Fatty Liver Disease  Earliest research focused on alcoholic fatty liver Diets require large amounts of dietary fat to produce effects. Lieberet al 2007 Lieber et al 2007
  6. 6. But what about humans?  1986- French and Nanji  Cirrhosis positively correlated with dietary polyunsaturated fats  Cirrhosis negatively associated with dietary saturated fats and cholesterol  1989- “Beef Fat Prevents Alcoholic Liver Disease in the Rat” “The correlation between the degree of histological abnormality and the linoleic acid content of the diet strongly implicates linoleic acid as an essential factor in the development of ALD.” Nanjiet al 1989
  7. 7. Non-Alcoholic Fatty Liver Disease  Diets high in corn oil cause fatty liver.  Replacing corn oil with medium chain fats reverses the condition. Roniset al 2013
  8. 8. What’s going on… Fats for fuel vs. fats for function “Essential Fatty Acids” “Essential” ≠ good fuel
  9. 9. What’s the problem: fuel vs. function  Problems with PUFA  Increased Reactive Oxygen Species Production  High peroxidation potential  Liver-saving Saturated Fats  Easy in easy out- no “first hit”  Increased Metabolism  Better Gut Integrity  Lower inflammation
  10. 10. Fish oil- a case study in fuel vs. function  Deficiency in long chain ω3s associated with Fatty Liver Disease.  Supplementation with fish oil reversed fatty liver in some patients.  BUT experimental models using large proportions of fish oil led to increased histopathology •ROS production •Peroxidizability •Cell-signaling •Insulin sensitizing effects
  11. 11. Pulling it all together…  Is it the fats’ fault?  What might we do with this information?
  12. 12. Thank you