# PLINs-mediated organelle interactions: a key of exercise-mediated improvement of skeletal muscle lipid metabolism disorders

**Authors:** Zhiyuan Liu, Yungang Zhao

PMC · DOI: 10.3389/fendo.2025.1700668 · Frontiers in Endocrinology · 2025-11-03

## TL;DR

This study explores how different types of exercise affect lipid metabolism in skeletal muscle through perilipin proteins, offering insights for treating metabolic disorders.

## Contribution

The study reveals how perilipin-mediated organelle interactions are modulated by exercise types to improve lipid metabolism in skeletal muscle.

## Key findings

- Acute exercise depletes lipid droplets coated with Perilipin 2 and 5 and induces relocalization of perilipin proteins.
- Moderate-intensity continuous training upregulates perilipin 2 and 5 expression, while high-intensity interval training enhances perilipin5 expression.
- Exercise-induced perilipin changes foster lipid droplet-mitochondria interactions, reducing ectopic lipid accumulation.

## Abstract

Perilipins are essential structural proteins localized on the surface of lipid droplets, with perilipin 2, 3, and 5 exhibiting specific expression in skeletal muscle. Intramuscular lipids are predominantly stored within lipid droplets, tightly regulated by perilipins. Perilipin 3 primarily governs lipid droplet biogenesis, whereas Perilipin 2 and PLIN5 play critical roles in mediating lipolysis through lipid droplet-organelle interactions and in responding to exercise-induced signaling cascades. Acute exercise selectively depletes lipid droplets coated with Perilipin 2 and Perilipin 5 while inducing subcellular relocalization of perilipin proteins. In contrast, moderate-intensity continuous training and high-intensity interval training elicit adaptive alterations in skeletal muscle perilipins protein expression: Moderate-intensity continuous training significantly upregulates perilipin 2 and 5 expression, whereas high-intensity interval training specifically enhances perilipin5 expression, fostering enhanced physical interactions between lipid droplets and mitochondria, thereby mitigating ectopic lipid accumulation. This study elucidates the intricate regulatory mechanisms of perilipin-mediated organelle interactions under diverse exercise modalities and their contributions to optimizing skeletal muscle lipid metabolism, providing a robust theoretical framework for developing targeted exercise-based interventions and potential therapeutic targets for metabolic disorders.

## Linked entities

- **Genes:** PLIN2 (perilipin 2) [NCBI Gene 123], PLIN3 (perilipin 3) [NCBI Gene 10226], PLIN5 (perilipin 5) [NCBI Gene 440503]
- **Proteins:** PLIN2 (perilipin 2), PLIN3 (perilipin 3), PLIN5 (perilipin 5)

## Full-text entities

- **Genes:** PLIN5 (perilipin 5) [NCBI Gene 440503] {aka LSDA5, LSDP5, MLDP, OXPAT}, PLIN2 (perilipin 2) [NCBI Gene 123] {aka ADFP, ADRP}, PLIN3 (perilipin 3) [NCBI Gene 10226] {aka M6PRBP1, PP17, TIP47}, PLIN1 (perilipin 1) [NCBI Gene 5346] {aka FPLD4, PERI, PLIN}
- **Diseases:** metabolic disorders (MESH:D008659)
- **Chemicals:** lipid (MESH:D008055)

## Full text

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## Figures

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## References

112 references — full list in the complete paper: https://tomesphere.com/paper/PMC12620214/full.md

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Source: https://tomesphere.com/paper/PMC12620214