Mouse muscle mTORC1 activation raises inflammation but not glucose intolerance
In mice, chronic mTORC1 activation in skeletal muscle increased inflammatory markers but was not sufficient to impair glucose tolerance, even on a Western diet. [1]
Automatic summary · not editorially reviewed
The key findings
Six-month-old female and male mice with tamoxifen-inducible, muscle-specific Depdc5 knockout were fed normal chow or a Western diet for 12 weeks. [1]
The knockout had minimal effects on fasting glucose, insulin, HOMA-IR, HbA1c or oral glucose tolerance, though female knockout mice showed a modest increase in diet-induced weight gain and fasting glucose. [1]
The knockout increased TNF-α and IL-6 protein expression and shifted macrophage polarization toward an M2-like phenotype without altering total macrophage content. [1]
The source at a glance
- Study type / format
- Experimental mouse study (abstract)
- Population / context
- Six-month-old female and male mice with muscle-specific Depdc5 knockout.
- Summary based on
- Study abstract
- Original publication
- July 17, 2026
Mouse muscle Depdc5 knockout and diet design
The abstract describes a mouse study testing whether chronic mTORC1 activation in skeletal muscle directly causes glucose intolerance. Six-month-old female and male mice with tamoxifen-inducible, muscle-specific knockout of Depdc5, a negative regulator of mTORC1, were fed normal chow or a Western diet (45% fat, 17% sucrose) for 12 weeks. The knockout increased mTORC1 signaling and altered autophagy markers.
Supporting source [1]
Glucose tolerance preserved despite inflammation
The Western diet increased body and fat mass and impaired glucose tolerance regardless of genotype. The knockout had minimal effects on fasting glucose, insulin, HOMA-IR, HbA1c or oral glucose tolerance, though female knockout mice showed a modest increase in diet-induced weight gain and fasting glucose. The knockout increased mitochondrial H2O2 production capacity without clear oxidative stress, and upregulated genes related to cell division and immune pathways, with higher TNF-α and IL-6 protein and a shift toward M2-like macrophages.
Supporting source [1]
Abstract-only scope of the mouse findings
The authors conclude that chronic mTORC1 activation in skeletal muscle promotes inflammatory remodeling but is insufficient to impair systemic glucose homeostasis, even under dietary stress. These are mouse findings from an abstract; the full text was not reviewed. The results do not establish effects on human lifespan or metabolic health, and associations described here come from an experimental mouse model, not from human studies.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings are from mice and do not establish human outcomes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Marchant ED, Kalenta H, Kilroe SP, May J, Martini WZ, Weldon KS, Lai Z, Rasmussen BB. · europepmc.org · July 17, 2026