This document discusses the role of dietary fats in fatty liver disease. It presents the "two-hit" theory of fatty liver disease development and examines major factors like alcohol, sugars, and fats that can contribute to fat accumulation in the liver. While early research focused on alcoholic fatty liver, more recent studies show that diets high in polyunsaturated fats like corn oil can cause non-alcoholic fatty liver disease, whereas replacing them with medium-chain fats can reverse the condition. Polyunsaturated fats may increase reactive oxygen species and peroxidation in the liver, whereas saturated fats are metabolized more easily without causing oxidative damage. The role of essential fatty acids is complex, as deficiency can contribute

1. Fatty Liver:
Is it the (dietary) fats’ fault?
Victoria Prince PhD, MSIV

2. Fatty Liver Disease
“2 hit” theory

3. Fatty Liver disease
Control
Alcohol-fed

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. 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. 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. 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. What’s going on…
Fats for fuel vs. fats for function
“Essential Fatty
Acids”
“Essential” ≠ good fuel

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. 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. Pulling it all together…
 Is it the fats’ fault?
 What might we do with this information?

12. Thank you
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