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Study · Animal study (in vivo) · mouse (aged female c57bl and 6) · 2026

8 results

Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress.

Xiao D, Cui X, Ali S, Li C, Wang B

Physiological research1 Aug 2026

PMID42708867 (opens in a new tab)PMCIDPMC13580669 (opens in a new tab)PepBankPUB-42708867
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Summary

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a major cause of cirrhosis, liver cancer, and cardiovascular disease. Early mitochondrial dysfunction drives lipid imbalance, inflammation, and fibrosis. Given the lack of approved pharmacological treatments, this study compares the mitochondria-targeted agents MitoQ and SS-31 for their effects on mitochondrial function, oxidative stress, apoptosis, and inflammation in aged, nutritionally stressed mice with MASLD. Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD. Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.). Liver tissues were analyzed by western blotting for mitochondrial biogenesis and dynamics markers (PGC-1?, NRF1, and TFAM), oxidative stress regulators (SOD2, Nrf2, 4-HNE), apoptosis-related proteins (Bax, and Bcl-2), inflammatory and fibrotic mediators (NF-?B, and NLRP3), and insulin signaling proteins (p-Akt, and GLUT2). Both MitoQ and SS-31 significantly improved mitochondrial protein expression and overall liver health compared with untreated MASLD mice. MitoQ primarily enhanced mitochondrial antioxidant defenses by upregulating SOD2 and Nrf2 while decreasing 4-HNE adduct formation, reflecting reduced oxidative damage. SS-31, in contrast, more effectively preserved mitochondrial structural integrity. Both compounds attenuated inflammation by suppressing NF-?B and NLRP3 activation. They also improved insulin sensitivity by increasing p-Akt and GLUT2 expression. Histological analysis using H&E staining revealed marked reductions in hepatic steatosis. Mitochondrial dysfunction drives MASLD progression. In aged MASLD mice, MitoQ enhances antioxidant defense, SS-31 preserves integrity, and both improve insulin signaling and reduce fibrosis, supporting mitochondrial therapy for MASLD.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In aged female mice with diet-induced MASLD, SS‑31 and MitoQ both significantly improved liver mitochondrial protein expression compared with untreated MASLD mice.

    In plain wordsIn mice with fatty liver disease, SS‑31 improved liver mitochondrial proteins compared with untreated mice.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseLiver mitochondrial protein expression
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    Both MitoQ and SS-31 significantly improved mitochondrial protein expression and overall liver health compared with untreated MASLD mice.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In aged female mice with diet-induced MASLD, SS‑31 and MitoQ both significantly improved overall liver health compared with untreated MASLD mice.

    In plain wordsIn mice with fatty liver disease, SS‑31 improved overall liver health compared with untreated mice.

    Peptide
    Elamipretide (SS-31)
    Outcome
    Direction not reportedOverall liver health
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    overall liver health compared with untreated MASLD mice.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  3. 03AnimalAnimal study (in vivo)Mechanism

    In aged female mice with diet-induced MASLD, SS‑31 preserved mitochondrial structural integrity more effectively than MitoQ.

    In plain wordsIn mice with fatty liver disease, SS‑31 kept mitochondrial structure intact better than MitoQ.

    Peptide
    Elamipretide (SS-31)
    Outcome
    Direction not reportedPreservation of mitochondrial structural integrity
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    MitoQ
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    SS-31, in contrast, more effectively preserved mitochondrial structural integrity.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  4. 04AnimalAnimal study (in vivo)Mechanism

    In aged female mice with diet-induced MASLD, SS‑31 and MitoQ both suppressed liver NF-kB activation.

    In plain wordsIn mice with fatty liver disease, SS‑31 lowered a liver inflammation signal (NF-kB).

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseNF-kB activation
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    Both compounds attenuated inflammation by suppressing NF-?B and NLRP3 activation.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  5. 05AnimalAnimal study (in vivo)Mechanism

    In aged female mice with diet-induced MASLD, SS‑31 and MitoQ both suppressed liver NLRP3 activation.

    In plain wordsIn mice with fatty liver disease, SS‑31 lowered a liver inflammation signal (NLRP3).

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseNLRP3 activation
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    Both compounds attenuated inflammation by suppressing NF-?B and NLRP3 activation.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  6. 06AnimalAnimal study (in vivo)Mechanism

    In aged female mice with diet-induced MASLD, SS‑31 and MitoQ both increased liver p-Akt expression, with improved insulin sensitivity.

    In plain wordsIn mice with fatty liver disease, SS‑31 raised a liver insulin-signaling protein (p-Akt).

    Peptide
    Elamipretide (SS-31)
    Outcome
    Increasep-Akt expression (insulin signaling)
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    They also improved insulin sensitivity by increasing p-Akt and GLUT2 expression.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  7. 07AnimalAnimal study (in vivo)Mechanism

    In aged female mice with diet-induced MASLD, SS‑31 and MitoQ both increased liver GLUT2 expression, with improved insulin sensitivity.

    In plain wordsIn mice with fatty liver disease, SS‑31 raised a liver glucose transporter (GLUT2).

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseGLUT2 expression (insulin signaling)
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    They also improved insulin sensitivity by increasing p-Akt and GLUT2 expression.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In aged female mice with diet-induced MASLD, histology showed marked reductions in hepatic steatosis after treatment.

    In plain wordsIn mice with fatty liver disease, liver tissue under the microscope showed marked reductions in liver fat after treatment with SS‑31 or MitoQ.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseHepatic steatosis (H&E histology)
    Study

    mouse (aged female C57BL/6)n: not reported in source

    High-fat, high-fructose diet-induced MASLD
    Comparator
    Untreated MASLD mice
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    3 mg/kg/day · intraperitonealAs given in this study (mouse (aged female C57BL/6)).

    Source sentences

    Summary
    Histological analysis using H&E staining revealed marked reductions in hepatic steatosis.
    2 context sentences
    Summary · context
    Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD.
    Summary · context
    Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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