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Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
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Hepatocyte-specific eNOS deletion impairs exercise-induced adaptations in hepatic mitochondrial function and
Rory P Cunningham1,2, Mary P Moore1,2, Ryan J Dashek1,3
1Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.
Obesity (Silver Spring, Md.)
|March 31, 2022
Summary
Endothelial nitric oxide synthase (eNOS) in liver cells is crucial for exercise to improve fat burning in male mice. Exercise benefits related to energy sensing and autophagy are reduced when eNOS is absent in these cells.
Area of Science:
- Exercise physiology
- Mitochondrial biology
- Hepatocyte function
Background:
- Endothelial nitric oxide synthase (eNOS) plays a role in cellular adaptations.
- Exercise is known to induce beneficial changes in liver mitochondria.
Purpose of the Study:
- To investigate the role of hepatocyte eNOS in exercise-induced hepatic mitochondrial adaptations.
- To determine the impact of hepatocyte-specific eNOS deletion on exercise responses in male and female mice.
Main Methods:
- Used hepatocyte-specific eNOS knockout (eNOShep-/-) and wild-type (eNOSfl/fl) male and female mice.
- Mice underwent voluntary wheel-running exercise (EX) or remained sedentary for 10 weeks.
- Assessed hepatic steatosis, hydrogen peroxide emission, fatty acid oxidation, and key signaling pathways (AMPK, mTOR, ULK1).
Main Results:
- Exercise resolved hepatic steatosis in male eNOShep-/- mice and ablated elevated hydrogen peroxide emission.
- Exercise-induced increases in [1-14C] palmitate oxidation were blunted in male eNOShep-/- mice.
- eNOShep-/- mice showed reduced markers of energy sensing (AMPK, mTOR) and autophagy initiation (ULK1).
- Female mice exhibited increased mitochondrial biogenesis markers regardless of eNOS status.
Conclusions:
- Hepatocyte eNOS is required for exercise-induced increases in hepatic fatty acid oxidation in male mice.
- Hepatocyte eNOS deletion impairs cellular energy sensing and autophagy activation.
- This study highlights a novel role for hepatocyte eNOS in exercise-mediated hepatic mitochondrial adaptations.
