# PLIN5 Promotes Lipid Reconstitution in Goat Intramuscular Fat via the PPARγ Signaling Pathway

## TL;DR

This study shows how PLIN5, a lipid droplet protein, affects fat accumulation in goat muscle, which could help improve meat quality.

## Contribution

The study reveals that PLIN5 regulates lipid deposition in goat intramuscular fat via PPARγ and PI3K-AKT signaling pathways.

## Key findings

- PLIN5 promotes lipid deposition in goat intramuscular fat by upregulating PPARγ and lipogenesis-related genes.
- LPI (18:0) and LPI (16:0) lipids are linked to PPARγ activation in intramuscular fat regulation.
- Inhibition of PI3K-AKT and PPARγ confirmed their roles in regulating cell proliferation and lipid accumulation.

## Abstract

Goat muscle intramuscular fat (IMF) is associated with the proliferation and differentiation of intramuscular precursor adipocytes, and IMF has various effects on meat quality. PLIN5 is a lipid droplet protein that plays an important role in lipid metabolism. However, the specific function and intrinsic mechanism of PLIN5 in goat IMF deposition remain unclear. Therefore, in this study, we clarified the function and potential mechanism of PLIN5 in goat intramuscular precursor adipocytes via experimental techniques such as overexpression, interference, untargeted lipid omics sequencing, inhibitor addition, and so on. It was found that PLIN5 regulates intramuscular lipid deposition in goat muscle via PPARγ and regulates intramuscular cell proliferation via the PI3K-AKT signaling pathway, thereby altering IMF. Untargeted lipidomic sequencing indicated that the differential lipids LPI (18:0) and LPI (16:0) may be involved in the activation of the PPARγ signaling pathway. These findings elucidate the potential regulatory mechanism of PLIN5 on IMF deposition and provide a theoretical basis for improving meat quality by targeting and regulating IMF deposition, which is important in breeding to improve goat meat quality.

Intramuscular fat (IMF) content is an important factor of goat meat quality, which is related to the proliferation and differentiation of intramuscular preadipocytes. Perilipin 5 (PLIN5) is a lipid droplet-associated protein; however, the specific function and underlying mechanism of PLIN5 in goat IMF deposition are still unclear. In this study, overexpression of PLIN5 significantly enhanced apoptosis and reduced the proliferation of preadipocytes and also promoted cellular lipid deposition via both the upregulation of the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and a significant increase in the expression of lipogenesis-related genes. The inhibition of PLIN5 then confirmed these results. Untargeted lipidomics sequencing identified a total of 34 differentially expressed lipids after PLIN5 overexpression in goat preadipocytes and analysis by KEGG pathway enrichment, which are mainly involved in the PI3K-AKT signaling pathway. The lipid omics findings also show that ceramides and lysophosphatidylinositol were significantly upregulated, e.g., Cer (d35:1), Cer (d18:2/22:1), LPI (18:0), and LPI (16:0), after overexpression of the PLIN5 gene. Higher expression of LPI (16:0) or LPI (18:0) may regulate lipid droplet accumulation by activating PPARγ. Rescue experiments with the PI3K-AKT inhibitor (LY294002) and the PPARγ inhibitor (GW9662) showed that the PI3K-AKT signaling pathway is involved in the regulation of cell proliferation, and PPARγ is involved in the regulation of lipid deposition. In conclusion, our findings demonstrate that PLIN5 regulates lipid reconstitution in goat intramuscular fat via PPARγ and PI3K-AKT signaling pathways. This regulation delivered theoretical support for improving meat quality from the aspect of IMF deposition.