ahs13 victoria prince fatty liver -- is it the fat's fault?
TRANSCRIPT
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Victoria Prince PhD, MSIV
Fatty Liver: Is it the (dietary) fats’ fault?
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Fatty Liver Disease
“2 hit” theory
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Fatty Liver diseaseControl Alcohol-fed
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How does the fat get there?
Synthesis
Export
Metabolism
Major Factors•Alcohol•Sugars•Fats•Nutrient Deficiency•Vitamin D (?)•Microbiota•Inflammation
Cohen et al 2011
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Models of Fatty Liver DiseaseEarliest research focused on alcoholic fatty
liver
Lieber et al 2007
Diets require large amounts of dietary fat to produce effects.
Lieber et al 2007
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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”
Nanji et al 1989
“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.”
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Non-Alcoholic Fatty Liver Disease
Diets high in corn oil cause fatty liver. Replacing corn oil with medium chain fats
reverses the condition.
Ronis et al 2013
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What’s going on…Fats for fuel vs. fats for function
“Essential Fatty Acids”
“Essential” ≠ good fuel
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What’s the problem: fuel vs. functionProblems with PUFA
Increased Reactive Oxygen Species Production
High peroxidation potentialLiver-saving Saturated Fats
Easy in easy out- no “first hit”Increased MetabolismBetter Gut Integrity Lower inflammation
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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
•Cell-signaling•Insulin sensitizing effects
•ROS production•Peroxidizability
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Pulling it all together…Is it the fats’ fault?What might we do with this information?
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Thank you
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