MOTS-c · research summary

MOTS-c partially protects against skeletal muscle deterioration in C26 cachexia.

Frontiers in medicine · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Pre-clinical in vitro and in vivo study using differentiated myotubes and C26 tumor-bearing mice
“Differentiated myotubes were treated with MOTS-c (50 μM) to assess intracellular signaling. In vivo, male mice were inoculated with Colon-26 (C26) carcinoma cells and treated daily with MOTS-c (15 mg/kg/2x Day, i.p.) or vehicle.”

Subjects

Differentiated myotubes and 12-week-old male CD2F1 mice inoculated with C26 colon adenocarcinoma cells
“In order to investigate the effect of MOTS-c on musculoskeletal health in cachectic animals, 12-week-old CD2F1 (purchased from Inotiv, West Lafayette, IN, United States) were randomized into four group: controls (n = 5), MOTS-c (n = 5), C26 (n = 8) and C26 + MOTS-c (n = 8).”

Sample size

26 mice total (5 controls, 5 MOTS-c only, 8 C26 tumor, 8 C26 + MOTS-c) plus in vitro myotube cultures
“12-week-old CD2F1 (purchased from Inotiv, West Lafayette, IN, United States) were randomized into four group: controls (n = 5), MOTS-c (n = 5), C26 (n = 8) and C26 + MOTS-c (n = 8).”

Duration

Approximately 14 days from tumor inoculation to euthanasia
“MOTS-c (15 mg/kg) (GenScript Inc., Piscataway, United States) was administered intraperitoneally (IP) the same day as tumor inoculation and twice daily until sacrifice (~day 14).”

Reported findings

MOTS-c treatment preserved skeletal muscle mass (quadriceps) in tumor-bearing mice despite not preventing total body weight loss
“Although MOTS-c did not prevent total body weight or fat loss, it significantly preserved skeletal muscle mass, rescuing quadriceps weight (+12% vs. C26 vehicle; p < 0.05) and trending toward protection of gastrocnemius mass and EDL function.”
MOTS-c attenuated the upregulation of atrogenes (Atrogin-1 and MuRF1) and modulated FOXO signaling pathways
“Cachexia-induced upregulation of Atrogin-1 (+8.6-fold) and MuRF1 (+16-fold) was attenuated by MOTS-c, accompanied by increased inhibitory pFOXO1 (+80%), reduced pFOXO3a (−39%), and partial restoration of PGC-1α protein (+143%).”
In vitro, MOTS-c increased PGC-1α mRNA expression and AMPK phosphorylation in myotubes
“In vitro, MOTS-c increased PGC-1α mRNA (+84.6%) and AMPK phosphorylation (+103.1%).”

Limitations stated by the authors

Study did not compare MOTS-c with other therapeutics, did not assess food intake, and treatment began at tumor inoculation rather than after cachexia onset
“We did not compare MOTS-c with other mitochondrial-targeted therapeutics, such as MitoQ, nor did we assess food intake, which may influence cachectic outcomes. Additionally, MOTS-c administration began at tumor inoculation; because clinical cachexia is typically treated after disease diagnosis and symptom onset, future studies should evaluate the therapeutic efficacy of MOTS-c when administered after cachexia has already developed.”

Source: PubMed 42266945 · DOI 10.3389/fmed.2026.1838178 · all study summaries

Study type

Pre-clinical in vitro and in vivo study using differentiated myotubes and C26 tumor-bearing mice

“Differentiated myotubes were treated with MOTS-c (50 μM) to assess intracellular signaling. In vivo, male mice were inoculated with Colon-26 (C26) carcinoma cells and treated daily with MOTS-c (15 mg/kg/2x Day, i.p.) or vehicle.”

Subjects

Differentiated myotubes and 12-week-old male CD2F1 mice inoculated with C26 colon adenocarcinoma cells

“In order to investigate the effect of MOTS-c on musculoskeletal health in cachectic animals, 12-week-old CD2F1 (purchased from Inotiv, West Lafayette, IN, United States) were randomized into four group: controls (n = 5), MOTS-c (n = 5), C26 (n = 8) and C26 + MOTS-c (n = 8).”

Reported findings

MOTS-c treatment preserved skeletal muscle mass (quadriceps) in tumor-bearing mice despite not preventing total body weight loss

“Although MOTS-c did not prevent total body weight or fat loss, it significantly preserved skeletal muscle mass, rescuing quadriceps weight (+12% vs. C26 vehicle; p < 0.05) and trending toward protection of gastrocnemius mass and EDL function.”

MOTS-c attenuated the upregulation of atrogenes (Atrogin-1 and MuRF1) and modulated FOXO signaling pathways

“Cachexia-induced upregulation of Atrogin-1 (+8.6-fold) and MuRF1 (+16-fold) was attenuated by MOTS-c, accompanied by increased inhibitory pFOXO1 (+80%), reduced pFOXO3a (−39%), and partial restoration of PGC-1α protein (+143%).”

In vitro, MOTS-c increased PGC-1α mRNA expression and AMPK phosphorylation in myotubes

“In vitro, MOTS-c increased PGC-1α mRNA (+84.6%) and AMPK phosphorylation (+103.1%).”

Limitations stated by the authors

Study did not compare MOTS-c with other therapeutics, did not assess food intake, and treatment began at tumor inoculation rather than after cachexia onset

“We did not compare MOTS-c with other mitochondrial-targeted therapeutics, such as MitoQ, nor did we assess food intake, which may influence cachectic outcomes. Additionally, MOTS-c administration began at tumor inoculation; because clinical cachexia is typically treated after disease diagnosis and symptom onset, future studies should evaluate the therapeutic efficacy of MOTS-c when administered after cachexia has already developed.”