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Updated: Apr 22, 2026
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
The Murphy Roths Large (MRL) mouse strain is naturally resistant to high fat diet-induced hyperglycemia
Aaron J Mull1, Tirsit K Berhanu1, Nathan W Roberts1
1Department of Physiology and Biophysics, The University of Illinois at Chicago, Chicago, IL 60612, USA.
Objective:
Due to their previously identified naturally and chronically increased levels of skeletal muscle pAMPK we hypothesized and now investigated whether the MRL/MpJ (MRL) mice would be resistant to high fat diet (HFD)-induced metabolic changes.
Materials/Methods:
Three-week old male MRL and control C57Bl/6 (B6) mice were randomly assigned to 12weeks of high fat diets (HFD) or control diets (CD). Weekly animal masses and fasting blood glucose measurements were acquired. During the last week of diet intervention, fasted animals were subjected to glucose and insulin tolerance tests. At harvest, tissues were dissected for immunoblots and serum was collected for ELISA assays.
Results:
The MRL mouse strain is known for its ability to regenerate ear punch wounds, cardiac cryoinjury, and skeletal muscle disease. Despite gaining weight and increasing their fat deposits the MRL mice were resistant to all other indicators of HFD-induced metabolic alterations assayed. Only the HFD-B6 mice displayed fasting hyperglycemia, hyperinsulinemia and hypersensitivity to glucose challenge. HFD-MRL mice were indistinguishable from their CD-MRL counterparts in these metrics. Skeletal muscles from the HFD-MRL contained heightened levels of pAMPK, even above their CD counterparts.
Conclusions:
The MRL mouse strain is the first naturally occurring mouse strain that we are aware of that is resistant to HFD-induced metabolic changes. Furthermore, the increased pAMPK suggests a proximal mechanism for these beneficial metabolic differences. We further hypothesize that these metabolic differences and plasticity provide the basis for the MRL mouse strain's super healing characteristics. This project's ultimate aim is to identify novel therapeutic targets, which specifically increase pAMPK.
Insights
MRL mice resist high-fat diet metabolic changes due to naturally high pAMPK levels. This suggests a new therapeutic target for metabolic disorders and enhanced healing.
Area of Science:
- Metabolic research
- Mouse models
- Physiology
Background:
- MRL/MpJ (MRL) mice exhibit naturally elevated skeletal muscle pAMPK.
- High-fat diet (HFD)-induced metabolic changes are a significant health concern.
Purpose of the Study:
- To investigate if MRL mice are resistant to HFD-induced metabolic alterations.
- To explore the role of pAMPK in metabolic health.
Main Methods:
- MRL and C57Bl/6 (B6) mice were fed HFD or control diets for 12 weeks.
- Weekly body mass and fasting blood glucose were measured.
- Glucose and insulin tolerance tests were performed; tissues and serum were analyzed.
Main Results:
- MRL mice, despite weight gain, were resistant to HFD-induced hyperglycemia and hyperinsulinemia.
- HFD-fed MRL mice showed metabolic profiles similar to control-fed MRL mice.
- Skeletal muscle in HFD-MRL mice had elevated pAMPK levels.
Conclusions:
- MRL mice are a novel naturally occurring strain resistant to HFD metabolic changes.
- Increased pAMPK is a likely mechanism for these beneficial effects.
- This finding may lead to new therapeutic targets for metabolic diseases and enhanced healing.
