Victoria Prince PhD, MSIV

Fatty Liver: Is it the (dietary) fats’ fault?

Fatty Liver Disease

“2 hit” theory

Fatty Liver diseaseControl Alcohol-fed

How does the fat get there?

Synthesis

Export

Metabolism

Major Factors•Alcohol•Sugars•Fats•Nutrient Deficiency•Vitamin D (?)•Microbiota•Inflammation

Cohen et al 2011

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

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.”

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

What’s going on…Fats for fuel vs. fats for function

“Essential Fatty Acids”

“Essential” ≠ good fuel

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

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

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

Thank you

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