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Updated: Jun 3, 2026

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Diminished AMPK signaling response to fasting in thioredoxin-interacting protein knockout mice
Allen M Andres1, Eric P Ratliff, Sowbarnika Sachithanantham
1Department of Biology, BioScience Center, San Diego State University, San Diego, CA 92182, USA.
Abstract:
Thioredoxin-interacting protein (Txnip) knockout (TKO) mice exhibit impaired response to fasting. Herein, we showed that activation of adenine monophosphate-activated protein kinase and cellular AMP levels were diminished in the heart and soleus muscle but not in gastrocnemius muscle of fasting TKO mice. Similarly, glycogen content in fasted TKO mice was increased in oxidative muscles but was not different in glycolytic muscles. These data suggest Txnip deficiency has a higher impact on oxidative muscle than glycolytic muscles and provide new insights into the metabolic role of Txnip.
Insights
Thioredoxin-interacting protein (Txnip) knockout mice show impaired fasting responses, particularly in oxidative muscles. Txnip deficiency affects AMP-activated protein kinase and glycogen levels, highlighting its metabolic role.
Area of Science:
- Metabolic regulation
- Muscle physiology
- Molecular biology
Background:
- Thioredoxin-interacting protein (Txnip) is implicated in cellular metabolism.
- Txnip knockout (TKO) mice display altered physiological responses.
- Fasting triggers significant metabolic shifts in mammals.
Purpose of the Study:
- To investigate the metabolic role of Txnip during fasting.
- To compare the impact of Txnip deficiency on oxidative versus glycolytic muscles.
Main Methods:
- Assessment of adenine monophosphate-activated protein kinase (AMPK) activation.
- Measurement of cellular AMP levels.
- Quantification of muscle glycogen content in fasting TKO mice and controls.
Main Results:
- AMPK activation and cellular AMP levels were reduced in the heart and soleus (oxidative) muscle of fasting TKO mice.
- Glycogen content was elevated in oxidative muscles of fasting TKO mice.
- These metabolic alterations were not observed in the gastrocnemius (glycolytic) muscle.
Conclusions:
- Txnip deficiency significantly impacts the metabolic adaptation to fasting in oxidative muscles.
- Txnip plays a crucial role in regulating energy metabolism, particularly in oxidative tissues.
- These findings provide novel insights into the differential metabolic functions of Txnip in various muscle types.
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