Single-nucleus Transcriptomics Reveal the Cytological Mechanism of Conjugated Linoleic Acids in Regulating Intramuscular Fat Deposition in Skeletal Muscles

Core Concepts

Conjugated linoleic acids (CLAs) can promote the transformation of fast glycolytic myofibers into slow oxidative myofibers and increase the percentage of SCD+/DGAT2+ adipocytes, which differentiate from PDE4D+/PDE7B+ preadipocytes, to enhance intramuscular fat deposition in skeletal muscles.

Abstract

This study utilized single-nucleus RNA sequencing (snRNA-seq) to investigate the cytological mechanism of CLAs in regulating intramuscular fat (IMF) deposition in skeletal muscles using pig models.
Key findings:

CLAs promoted the transformation of fast glycolytic myofibers into slow oxidative myofibers by upregulating the expression of genes involved in oxidative metabolism and downregulating glycolysis-related genes.
CLAs increased the percentage of SCD+/DGAT2+ adipocytes, which are the main contributors to IMF deposition, by promoting the differentiation of PDE4D+/PDE7B+ preadipocytes.
Pseudotemporal trajectory and RNA velocity analyses verified that PDE4D+/PDE7B+ preadipocytes could differentiate into SCD+/DGAT2+ and FABP5+/SIAH1+ adipocytes.
CLAs facilitated the differentiation of fibro/adipogenic progenitors (FAPs) into SCD+/DGAT2+ adipocytes by inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway.

These findings provide insights into the cytological mechanism of CLAs in regulating IMF deposition and offer potential opportunities to use pigs as animal models for studying human muscle-related diseases.

Stats

Compared with the control group, the CLA group had a higher proportion of type I (22.01% vs. 17.54%) and type IIA (7.52% vs. 3.64%) myofibers, but a lower proportion of type IIX (3.87% vs. 10.09%) and type IIB (59.35% vs. 63.88%) myofibers.
The proportion of SCD+/DGAT2+ adipocytes was higher in the CLA group (82.31% vs. 79.37%), while the proportion of PDE4D+/PDE7B+ adipocytes was lower (11.19% vs. 14.81%).

Quotes

"CLAs could promote slow oxidative myofibers switch into fast glycolic myofibers in pig muscles."
"PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ and FABP5+/SIAH1+ adipocytes."
"CLAs may promote FAPs directed differentiation into SCD+/DGAT2+ adipocytes via inhibiting JNK signaling pathway."

Key Insights Distilled From

Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

by Wang,L., Liu... at www.biorxiv.org 05-30-2024

https://www.biorxiv.org/content/10.1101/2024.05.30.596608v1

Deeper Inquiries

How can the findings from this study on pigs be translated to understand the effects of CLAs on human skeletal muscle and fat deposition

The findings from this study on pigs can provide valuable insights into understanding the effects of CLAs on human skeletal muscle and fat deposition. Pigs are often used as animal models in biomedical research due to their physiological similarities to humans, making the translation of results more feasible. The study identified that CLAs promoted the transformation of fast glycolytic myofibers into slow oxidative myofibers in pig muscles. This finding suggests that CLAs may have the potential to influence muscle fiber type composition in humans as well. Additionally, the study revealed the differentiation trajectories of adipocytes and fibro/adipogenic progenitors (FAPs) in response to CLAs, indicating a potential mechanism for regulating fat infiltration in skeletal muscles. These mechanisms could be relevant to understanding how CLAs may impact fat deposition in human skeletal muscle.

What are the potential limitations or confounding factors in using pigs as animal models for studying the effects of CLAs on muscle and fat metabolism

While using pigs as animal models for studying the effects of CLAs on muscle and fat metabolism has its advantages, there are also potential limitations and confounding factors to consider. One limitation is the species-specific response to CLAs, as the metabolic processes and physiological characteristics of pigs may differ from those of humans. This could lead to differences in the outcomes observed in pigs versus humans. Additionally, factors such as diet, environment, and genetic variability among individual pigs could introduce variability and confound the results. It is essential to carefully consider these factors when extrapolating findings from pig studies to human health.

Could the regulatory mechanisms identified in this study involving myofiber type transformation and adipocyte differentiation be targeted for the development of nutritional or pharmacological interventions to combat myosteatosis and other muscle-related diseases in humans

The regulatory mechanisms identified in this study, including myofiber type transformation and adipocyte differentiation, could be targeted for the development of nutritional or pharmacological interventions to combat myosteatosis and other muscle-related diseases in humans. For example, the promotion of slow oxidative myofibers over fast glycolytic myofibers by CLAs could be leveraged to improve muscle function and metabolic health in individuals with myosteatosis. Similarly, targeting the differentiation trajectories of adipocytes and FAPs, as influenced by CLAs, could offer new strategies for managing fat infiltration in skeletal muscles. By understanding and manipulating these regulatory mechanisms, novel interventions could be developed to address muscle-related diseases in humans.