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Experiment

Park2 LKO male HFD CLAMS
Summary Data Summary
Investigator Jurczak, Michael
Description Mitochondrial dysfunction is associated with many human diseases and results
from mismatch of damage and repair over the life of the organelle. PARK2 is a
ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that
selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo
models results in susceptibility to stress-induced mitochondrial and cellular
dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from
nutritional stress and do not develop obesity, hepatic steatosis or insulin
resistance when fed a high-fat diet (HFD). However, these phenomena are casually
related and the physiological basis for this phenotype is unknown. We therefore
undertook a series of acute HFD studies to more completely understand the
physiology of Park2 KO during nutritional stress. We find that intestinal lipid
absorption is impaired in Park2 KO mice as evidenced by increased fecal lipids
and reduced plasma triglycerides after intragastric fat challenge. Park2 KO mice
developed hepatic steatosis in response to intravenous lipid infusion as well as
during incubation of primary hepatocytes with fatty acids, suggesting that
hepatic protection from nutritional stress was secondary to changes in energy
balance due to altered intestinal triglyceride absorption. Park2 KO mice showed
reduced adiposity after 1-wk HFD, as well as improved hepatic and peripheral
insulin sensitivity. These studies suggest that changes in intestinal lipid
absorption may play a primary role in protection from nutritional stress in
Park2 KO mice by preventing HFD-induced weight gain and highlight the need for
tissue-specific models to address the role of PARK2 during metabolic stress.

Applicable research area(s): Diabetes, Obesity, Metabolism
Status Completed
Public Release 7/14/2018
Animal Age Measured In: week(s) post-natal (w)
Flags has-data-flagSame StrainMetadataExperiment Description
Data Analysis
TypeCount
Animals16
Experimental Conditions1
Catalog Items1
Curation Info (# flags)3
Phenotype Assays11
Phenotype Measurements176
Histology Images0
Publications0


Animals
Strain NameCommon NameFemalesMalesUnknown
C57BL/6
0
8
0
C57BL/6-Park2tm1Mjj Tg(Alb-Cre)21Mgn
0
8
0

Animals/Strains
Experimental Factors
 Categorical Values
Name / AbbreviationDescription

Experimental Factor: Experimental Group

 Control
This animal belongs to the control group for the experiment.
 Experiment
This animal belongs to experimental group that is homozygous for gene manipulations.
Experimental Factor (Units)
Experimental Group
Experimental Factor Values


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