# Omega‐3 fatty acid supplementation does not attenuate declines in skeletal muscle mitochondrial area in young, healthy females during immobilization

**Authors:** Megan M. Lo, Merryl N. Black, Chris McGlory, Ravninder Bahniwal, Michael Kamal, Joe Quadrilatero, Stuart M. Phillips, Michaela C. Devries

PMC · DOI: 10.14814/phy2.70736 · Physiological Reports · 2026-01-23

## TL;DR

This study found that omega-3 fatty acid supplementation does not prevent the loss of mitochondrial area in skeletal muscle of young, healthy females during leg immobilization.

## Contribution

The study reveals that omega-3 supplementation does not prevent immobilization-induced mitochondrial loss in specific muscle regions.

## Key findings

- Subsarcolemmal mitochondrial content decreased significantly during immobilization and remained low after recovery.
- Omega-3 supplementation did not prevent the decline in subsarcolemmal mitochondrial content.
- Intermyofibrillar mitochondrial content was lower than baseline after recovery, but not during immobilization.

## Abstract

Mitochondrial subcellular area influences function. Muscle disuse reduces mitochondrial content; however, its effect on mitochondrial subcellular location is unclear. Omega‐3 fatty acid (n‐3) attenuates declines in muscle mass and mitochondrial function during disuse; however, whether n‐3 supplementation prevents the decline in mitochondrial content has not been examined. We investigated the effects of 2 weeks of leg immobilization followed by 2 weeks of remobilization on skeletal muscle mitochondrial content and subcellular localization with and without n‐3 supplementation. Twenty healthy females supplemented with n‐3 (2.97 g EPA and 2.03 g DHA) or control (isoenergetic sunflower oil) during 2 weeks of unilateral leg immobilization and 2 weeks of remobilization. Vastus lateralis biopsies were taken for electron microscopic analysis of mitochondrial content. Subsarcolemmal (SS) mitochondrial content decreased during immobilization (control: −9%, n‐3: −66%, p = 0.009) and remained lower following recovery (control: −41%, n‐3: −42%, p = 0.005). This effect was driven by the n‐3 group (p < 0.02). Intermyofibrillar (IMF) mitochondrial content did not decline during immobilization, but was lower than baseline following recovery in the central (p = 0.01) IMF. The effects of leg immobilization on mitochondrial content differ by location, are not reversed with short‐term recovery, and are influenced by n‐3 supplementation.

## Linked entities

- **Chemicals:** EPA (PubChem CID 446284), DHA (PubChem CID 15608515)

## Full-text entities

- **Genes:** Pax7 (paired box 7) [NCBI Gene 500574] {aka RGD1564360}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, BNIP3 (BCL2 interacting protein 3) [NCBI Gene 664] {aka HABON, NIP3}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, FIS1 (fission, mitochondrial 1) [NCBI Gene 51024] {aka CGI-135, TTC11}, OPA1 (OPA1 mitochondrial dynamin like GTPase) [NCBI Gene 4976] {aka BERHS, MGM1, MTDPS14, MTDPS14A, MTDPS14B, NPG}, Sqstm1 (sequestosome 1) [NCBI Gene 113894] {aka Osi, ZIP, ZIP3}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, MAP1LC3B (microtubule associated protein 1 light chain 3 beta) [NCBI Gene 81631] {aka ATG8F, LC3B, MAP1A/1BLC3, MAP1LC3B-a}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, Fdft1 (farnesyl diphosphate farnesyl transferase 1) [NCBI Gene 29580], BNIP3L (BCL2 interacting protein 3 like) [NCBI Gene 665] {aka BNIP3a, NIP3L, NIX}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], SQSTM1 (sequestosome 1) [NCBI Gene 8878] {aka A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** muscle atrophy (MESH:D009133), atrophy (MESH:D001284), mitochondrial dysfunction (MESH:D028361), loss of muscle mass and strength (MESH:C536030), thrombosis (MESH:D013927), Muscle disuse (MESH:D020966), inflammatory (MESH:D007249), muscle (MESH:D019042), Diabetes (MESH:D003920), injury to the (MESH:D014947)
- **Chemicals:** Long chain omega-3 (n-3) fatty acid (-), Omega-3 FA (MESH:D015525), lipid (MESH:D008055), FA (MESH:D005227), xylocaine (MESH:D008012), n (MESH:D009584), glutaraldehyde (MESH:D005976), ADP (MESH:D000244), SDS (MESH:D012967), bicinchoninic acid (MESH:C047117), bromophenol blue (MESH:D001978), DHA (MESH:C027493), oleic acid (MESH:D019301), NaCl (MESH:D012965), osmium tetroxide (MESH:D009993), Triton X-100 (MESH:D017830), carbon (MESH:D002244), Tween 20 (MESH:D011136), ethanol (MESH:D000431), glycerol (MESH:D005990), copper (MESH:D003300), ROS (MESH:D017382), PVDF (MESH:C024865), uranyl acetate (MESH:C005460)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Nicotiana tabacum (American tobacco, species) [taxon 4097]

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12830871/full.md

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Source: https://tomesphere.com/paper/PMC12830871