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Publication
Reduced intestinal lipid absorption and body weight-independent improvements in
insulin sensitivity in high-fat diet-fed Park2 knockout mice.
Authors Costa DK, Huckestein BR, Edmunds LR, Petersen MC, Nasiri A, Butrico GM, Abulizi
A, Harmon DB, Lu C, Mantell BS, Hartman DJ, Camporez JP, O'Doherty RM, Cline GW,
Shulman GI, Jurczak MJ
Submitted By Submitted Externally on 10/26/2016
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2016
Date Published
Volume : Pages 311 : E105 - 16
PubMed Reference 27166280
Abstract 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.




Strains




Genes
SymbolDescription
Park2parkin

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