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

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Presentation on theme: "Is Perk involved in the PPAR alpha adaptive response to fasting in the liver? Part I “Peroxisome proliferator-activated receptor alpha mediates the adaptive."— Presentation transcript:

1 Is Perk involved in the PPAR alpha adaptive response to fasting in the liver? Part I “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 a fatty liver (Oil Red Staining) -become hypoglycemic (Blood Glucose) -have significantly decreased levels of β-hydroxybutyrate (Kit) -have significantly higher Free Fatty Acids (Kit)

2 Liver Blood Fasting = Fatty acids are released from fat cells into the blood and transported to liver Gluconeogenesis =Glucose formation driven by fatty acid oxidation in the liver Glucose= released into blood system to fuel body Measure Blood Glucose Ketones = B hydroxybutyrate, released from liver during fatty acid oxidation Measure B Hydroxybutyrate in BloodMeasure Free Fatty Acids in Blood Lipid accumulation in the liver – Oil Red Staining = stains lipid Liver Phenotype = Color of liver

3 Blood glucose levels in Albumin-Cre Mice (3 mos.old) over 24 hours Mouse # (Sex)TypeTreatment0 hrs8 hrs16 hrs24 hrs (tail)24 hrs (heart) 16284 (M)KOFast166120117133185 16200 (M)KOFast15114113910878 16281 (F)KOFast12798937780 16064 (F)KOFast150124818073 Average Blood Glucose (mg/dL) KO Fasted148.5+16.1120.75+17.7107.5+25.899.5+26.3104+54.1 16058 (M) *2 mo oldWTFast112108128144119 16195 (F)WTFast13111110613486 16057 (F)WTFast1371237357147 Average Blood Glucose (mg/dL) WT Fasted126.7+13.1114.0+7.9102.3+27.7111.7+47.6117.3+30.5 16283 (M)KOFed126144130148274 16060 (M)KOFed209130146149108 16280 (F)KOFed117143132142265 16198 (F)KOFed151146131152167 Average Blood Glucose (mg/dL) KO Fed150.75+41.4140.75+7.3134.75+7.5147.75+4.2203.5+80 16199 (M)WTFed111145136152153 16034 (M) *4 mo oldWTFed130 139151294 16279 (F)WTFed139129124136214 Average Blood Glucose (mg/dL) WT Fed126.7+14.3134.7+9.0133.0+7.9146.3+9.0220.3+70.7

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