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Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2016 Jul 01; Vol. 311 (1), pp. E105-16. Date of Electronic Publication: 2016 May 10. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 the American Physiological Society.)
- Subjects :
- Animals
Energy Metabolism
Fatty Acids pharmacology
Fatty Liver genetics
Feces chemistry
Infusions, Intravenous
Intestinal Mucosa metabolism
Lipids analysis
Lipids pharmacology
Liver drug effects
Liver metabolism
Male
Mice
Mice, Knockout
Mitochondria metabolism
Mitophagy genetics
Triglycerides blood
Weight Gain genetics
Body Weight genetics
Diet, High-Fat
Insulin Resistance genetics
Intestinal Absorption genetics
Lipid Metabolism genetics
Ubiquitin-Protein Ligases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 311
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 27166280
- Full Text :
- https://doi.org/10.1152/ajpendo.00042.2016