Is Perk involved in the PPAR alpha adaptive response to fasting in the liver? Part II “Peroxisome proliferator-activated receptor alpha mediates the adaptive.

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Presentation transcript:

Is Perk involved in the PPAR alpha adaptive response to fasting in the liver? Part II “Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting” by Kersten, et al.~ Journal of Clinical Investigation, June 1999 PPAR alpha = known regulator of oxidation in the liver: *Fasted PPARα-null mice -have significantly higher Free Fatty Acids -have a fatty liver -become hypoglycemic -have significantly decreased levels of β-hydroxybutyrate

3. Assess lipid accumulation in the liver which may indicate a problem with fatty acid oxidation (Oil Red Stain) 4. Measure B hydroxybutyrate levels (ketone released from liver into the blood stream during fatty acid oxidation) – significantly decreased levels of ketones may indicate a problem with fatty acid oxidation (Kit) 2. Measure Free Fatty Acids (FFA) in blood to determine relative levels of FFA after fasting -significantly higher levels of FFA acids may indicate a problem with fatty acid uptake in the liver (Kit) 5. Measure Blood Glucose levels to determine how much glucose is released from the liver into the blood stream after gluconeogenesis (glucose formation driven by fatty acid oxidation in the liver) – decreased levels of glucose may indicate a problem with fatty acid oxidation 1. Fasting = Fatty acids are released from fat cells into the blood and are delivered to the liver for oxidation (Removed food for 24 hrs) Liver Blood

Mouse # (Sex)TypeTreatment (M)KOFast (M)KOFast (F)KOFast (F)KOFast (M) *2 mo oldWTFast (F)WTFast (F)WTFast (M)KOFed (M)KOFed (F)KOFed (F)KOFed (M)WTFed (M) *4 mo oldWTFed (F)WTFed Albumin-Cre Mice (Liver specific KO ~ 3 months old)

Free Fatty Acids in PPARalpha null mice vs Albumin-Cre KO mice

KO FastKO Fed WT FastWT Fed

KO Fast WT Fast PPAR alpha mice

Conclusions: Fasted Perk Liver Specific KO Mice -have a somewhat fatty liver (significantly different than Fasted WT?) -do NOT become hypoglycemic -do NOT have significantly decreased levels of β-hydroxybutyrate -do NOT have significantly higher Free Fatty Acids Do not seem to be directly involved in the PPAR alpha adaptive response to fasting in the liver THANKS FOR ALL YOUR HELP!!! Kaori, Sounak, Vivian