MOTS-c · research summary

Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells.

Inflammation and regeneration · 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

In vitro and in vivo experimental study
“We hypothesized that MOTS-c regulates MSC function in an obese state and employed an exogenous supplementation strategy to examine whether restoring MOTS-c levels can rescue obesity-induced MSC function, and elucidate its potential mechanism through in vitro and in vivo experiments.”

Subjects

Adipose-derived mesenchymal stromal cells from human donors with obesity or lean status, and 129-S1 mice with renal artery stenosis
“MSCs isolated from abdominal fat of patients with obesity (BMI ≥ 30 kg/m2) and lean donors (BMI < 30 kg/m2) (n = 6/group) were assessed in vitro for changes in proliferation, senescence (p16, p21) TNF-α, and antioxidant gene expression following MOTS-c co-incubation.”

Sample size

6 human donors per group and 6 mice per experimental group
“Individuals with or without (lean) obesity (n = 6 each), aged 18–80, were recruited as MSC donors at the Mayo Clinic in Rochester between February 2018 and January 2023.”

Reported findings

Exogenous MOTS-c reduced proliferation and increased senescence gene expression in obese MSCs
“Nevertheless, although exogenous MOTS-c restored intracellular levels and activated AMPK signaling in obese MSCs, it reduced proliferation, increased expression of senescence-associated genes (p16, p21), and upregulated TNF-α.”
MOTS-c pretreatment failed to improve renal perfusion or fibrosis in mice with renal artery stenosis
“In vivo, in a murine model of renal artery stenosis, MOTS-c-pretreated MSCs failed to improve renal perfusion, fibrosis, or tubular injury, while pretreatment also blunted the reparative efficacy of lean MSCs.”
Restoration of mitochondrial signaling did not reverse obesity-induced MSC dysfunction
“These findings reveal that restoration of mitochondrial metabolic signaling is insufficient to reverse obesity-induced MSC dysfunction and may paradoxically exacerbate senescence and inflammation.”

Limitations stated by the authors

Small sample size, lack of ethnic diversity, and potential mismatch between exogenous supplementation and physiological conditions
“Our study has certain limitations.”

Source: PubMed 42324588 · DOI 10.1186/s41232-026-00431-7 · all study summaries

Study type

In vitro and in vivo experimental study

“We hypothesized that MOTS-c regulates MSC function in an obese state and employed an exogenous supplementation strategy to examine whether restoring MOTS-c levels can rescue obesity-induced MSC function, and elucidate its potential mechanism through in vitro and in vivo experiments.”

Subjects

Adipose-derived mesenchymal stromal cells from human donors with obesity or lean status, and 129-S1 mice with renal artery stenosis

“MSCs isolated from abdominal fat of patients with obesity (BMI ≥ 30 kg/m2) and lean donors (BMI < 30 kg/m2) (n = 6/group) were assessed in vitro for changes in proliferation, senescence (p16, p21) TNF-α, and antioxidant gene expression following MOTS-c co-incubation.”

Reported findings

Exogenous MOTS-c reduced proliferation and increased senescence gene expression in obese MSCs

“Nevertheless, although exogenous MOTS-c restored intracellular levels and activated AMPK signaling in obese MSCs, it reduced proliferation, increased expression of senescence-associated genes (p16, p21), and upregulated TNF-α.”

MOTS-c pretreatment failed to improve renal perfusion or fibrosis in mice with renal artery stenosis

“In vivo, in a murine model of renal artery stenosis, MOTS-c-pretreated MSCs failed to improve renal perfusion, fibrosis, or tubular injury, while pretreatment also blunted the reparative efficacy of lean MSCs.”

Restoration of mitochondrial signaling did not reverse obesity-induced MSC dysfunction

“These findings reveal that restoration of mitochondrial metabolic signaling is insufficient to reverse obesity-induced MSC dysfunction and may paradoxically exacerbate senescence and inflammation.”