# Proteolytic markers associated with a gain and loss of leg muscle mass with resistance training followed by high-intensity interval training

PMID: 37589512
Journal: Experimental Physiology
Published: 2023 Oct
Authors: Michel JM, Godwin JS, Plotkin DL, Mesquita PHC, McIntosh MC, Ruple BA, Libardi CA, Mobley CB, Kavazis AN, Roberts MD

## Question

Do proteolytic markers increase when resistance-training-induced vastus lateralis hypertrophy is lost after a subsequent 7-week treadmill HIIT block?

## Summary

This secondary mechanistic analysis studied muscle biopsies from 11 untrained young men before training, after 7 weeks of resistance training, and after a subsequent 7 weeks of treadmill HIIT. The authors found that the previously observed loss of resistance-training-induced vastus lateralis size after HIIT coincided with higher proteolysis-related markers, but the paper provides limited HIIT protocol detail and does not report exercise safety or adherence outcomes.

## Population

- Untrained college-aged men with complete vastus lateralis biopsies at PRE, MID, and POST.
- Sample size: 11
- Age: 18-30 years eligible
- Sex: Male
- Fitness level: Untrained
- Health status: No known cardiometabolic disease; BMI <=30 kg/m2

## Methodology

- Secondary mechanistic pre-mid-post analysis of a single exercise sequence
- 14 weeks total: 7 weeks resistance training followed by 7 weeks treadmill HIIT
- University laboratory and training setting

## Protocol

- Resistance training followed by treadmill HIIT.
- Modality: Resistance training, then treadmill HIIT.
- Intensity: High-intensity; exact HIIT target not reported.
- Frequency: RT 2 days/week, then HIIT 3 days/week.
- Program length: 7 weeks RT plus 7 weeks HIIT.
- Progression: Not reported in this article; parent publication cited for training details.
- Within-person PRE and MID comparisons.
- Modality: Baseline and post-resistance-training testing.

## Outcomes

### Atrogene mRNA
Status: worse/safety concern
TRIM63, FBXO32, and FOXO3A were higher after HIIT than both baseline and post-RT.

POST vs PRE and MID p<0.05.

### Proteasome markers
Status: worse/safety concern
20S proteasome core abundance increased after HIIT; activity increased after RT and remained higher after HIIT.

20S core POST vs PRE p=0.031; POST vs MID p=0.049; activity MID and POST vs PRE p<0.05.

### Calpain/autophagy
Status: mixed
Calpain-2 and Beclin-1 increased at MID and POST, but interpretation as breakdown versus turnover was uncertain.

MID and POST vs PRE p<0.05 for calpain-2 and Beclin-1 protein levels.

### In vitro MPS
Status: worse/safety concern
IGF1+AICAR blunted IGF1-related myotube growth and had lower MPS proxy than IGF1 alone.

Myotube diameter p=0.017; puromycin/MPS proxy p<0.001.

## Practical Insights

- Do not use this paper as a direct HIIT workout template because interval details and safety outcomes are missing.
- For users focused on hypertrophy, this paper raises a hypothesis that switching from RT to HIIT may not maintain RT-induced muscle size in untrained men.
- The evidence is mechanistic and should not be framed as proof that HIIT alone causes muscle loss.

## Limitations

- Small sample of 11 men
- Secondary analysis
- No control or comparator exercise group
- No nontraining post-RT control
- No in vivo muscle protein synthesis or breakdown measures
- Exact HIIT protocol not reported in this article
- No adverse-event or adherence reporting

## Safety And Adherence

- The article did not report adverse events, injuries, symptoms, adherence, or tolerability for the training intervention.
- Participants were screened to exclude cardiometabolic disease and conditions contraindicating exercise training or muscle biopsy.
- Hydration was checked before testing sessions using urine specific gravity <=1.020 as a threshold to continue testing.
- Repeated vastus lateralis biopsies were part of the study procedures, but biopsy complications were not reported.

## Original Sources

- [PubMed](https://pubmed.ncbi.nlm.nih.gov/37589512/) (pubmed)
- [DOI](https://doi.org/10.1113/EP091286) (doi)
- [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543615/) (full text)

## Agent Guidance

Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.