Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals

Xiao, Li; Fu, Xiujuan; Yang, Gongshe; Du, Min

doi:10.1017/s175173111900209x

Cited by 66 publications

(54 citation statements)

References 113 publications

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“…Intramuscular fat (IMF) was regarded as the most intramuscular adipocytes deposited between primary and secondary muscle bundles of perimysium, and a small population was also founded within muscle bundles (Li et al, 2020). The IMF accumulation was mainly determined by the hyperplasia and hypertrophy of intramuscular adipocytes, indicated by an increase in the number and size of adipocytes, respectively (Haczeyni et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway

Xiong

Wang

et al. 2021

Front. Physiol.

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Intramuscular fat (IMF) deposition is one of the most important factors to affect meat quality in livestock and induce insulin resistance and adverse metabolic phenotypes for humans. However, the key regulators involved in this process remain largely unknown. Although liver kinase B1 (LKB1) was reported to participate in the development of skeletal muscles and classical adipose tissues. Due to the specific autonomic location of intramuscular adipocytes, deposited between or within muscle bundles, the exact roles of LKB1 in IMF deposition need further verified. Here, we cloned the goat LKB1 coding sequence with 1,317 bp, encoding a 438 amino acid peptide. LKB1 was extensively expressed in detected tissues and displayed a trend from decline to rise during intramuscular adipogenesis. Functionally, knockdown of LKB1 by two individual siRNAs enhanced the intramuscular preadipocytes differentiation, accompanied by promoting lipid accumulation and inducing adipogenic transcriptional factors and triglyceride synthesis-related genes expression. Conversely, overexpression of LKB1 restrained these biological signatures. To further explore the mechanisms, the RNA-seq technique was performed to compare the difference between siLKB1 and the control group. There were 1,043 differential expression genes (DEGs) were screened, i.e., 425 upregulated genes and 618 downregulated genes in the siLKB1 group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis predicted that the DEGs were mainly enriched in the focal adhesion pathway and its classical downstream signal, the PI3K-Akt signaling pathway. Specifically, knockdown of LKB1 increased the mRNA level of focal adhesion kinase (FAK) and vice versa in LKB1-overexpressed cells, a key component of the activated focal adhesion pathway. Convincingly, blocking this pathway by a specific FAK inhibitor (PF573228) rescued the observed phenotypes in LKB1 knockdown adipocytes. In conclusion, LKB1 inhibited goat intramuscular adipogenesis through the focal adhesion pathway. This work expanded the genetic regulator networks of IMF deposition and provided theoretical support for improving human health and meat quality from the aspect of IMF deposition.

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Section: Introductionmentioning

confidence: 99%

LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway

Xiong

Wang

et al. 2021

Front. Physiol.

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“…Adipogenesis and subsequent lipid deposition in skeletal muscle constitute intramuscular fat mainly stored in adipocyte dispersed in the muscle fascicle. Excessive intramuscular fat accumulation not only undermines skeletal muscle functions and metabolic homeostasis in humans [ 8 , 9 ] but also endows muscle with marbling-related characteristics of economic value in farm animals [ 10 ]. Therefore, it is of great significance to elucidate mechanisms governing the balance of myogenesis and adipogenesis in skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs

Zhang

Sun

et al. 2020

Stem Cell Res Ther

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Background Skeletal muscle is a complex and heterogeneous tissue accounting for approximately 40% of body weight. Excessive ectopic lipid accumulation in the muscle fascicle would undermine the integrity of skeletal muscle in humans but endow muscle with marbling-related characteristics in farm animals. Therefore, the balance of myogenesis and adipogenesis is of great significance for skeletal muscle homeostasis. Significant DNA methylation occurs during myogenesis and adipogenesis; however, DNA methylation pattern of myogenic and adipogenic precursors derived from skeletal muscle remains unknown yet. Methods In this study, reduced representation bisulfite sequencing was performed to analyze genome-wide DNA methylation of adipogenic and myogenic precursors derived from the skeletal muscle of neonatal pigs. Integrated analysis of DNA methylation and transcription profiles was further conducted. Based on the results of pathway enrichment analysis, myogenic precursors were transfected with CACNA2D2-overexpression plasmids to explore the function of CACNA2D2 in myogenic differentiation. Results As a result, 11,361 differentially methylated regions mainly located in intergenic region and introns were identified. Furthermore, 153 genes with different DNA methylation and gene expression level between adipogenic and myogenic precursors were characterized. Subsequently, pathway enrichment analysis revealed that DNA methylation programing was involved in the regulation of adipogenic and myogenic differentiation potential through mediating the crosstalk among pathways including focal adhesion, regulation of actin cytoskeleton, MAPK signaling pathway, and calcium signaling pathway. In particular, we characterized a new role of CACNA2D2 in inhibiting myogenic differentiation by suppressing JNK/MAPK signaling pathway. Conclusions This study depicted a comprehensive landmark of DNA methylome of skeletal muscle-derived myogenic and adipogenic precursors, highlighted the critical role of CACNA2D2 in regulating myogenic differentiation, and illustrated the possible regulatory ways of DNA methylation on cell fate commitment and skeletal muscle homeostasis.

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“…The major evidence on the cross-talk between satellite cells and FAP essentially derives from animal studies, which not always resemble the processes occurring in humans (due to specie-specific differences in time frames and cellular components) [28]. However, satellite cell-FAP functional interactions have been reported in humans by studies on prolonged resistance exercise training effects or on myopathy [32][33][34][35]. Upon aberrant regulation, FAP, whose function is normally dedicated to muscle remodeling and regeneration, promote inflammation and tissue fibrosis [36].…”

Section: Skeletal Muscle Cell Remodeling: Not Only a Matter Of Sizementioning

confidence: 99%

Vitamin D Restores Skeletal Muscle Cell Remodeling and Myogenic Program: Potential Impact on Human Health

Crescioli

2021

IJMS

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Skeletal muscle cells, albeit classified as vitamin D receptor (VDR)-poor cells, are finely controlled by vitamin D through genomic and non-genomic mechanisms. Skeletal muscle constantly undergoes cell remodeling, a complex system under multilevel regulation, mainly orchestrated by the satellite niche in response to a variety of stimuli. Cell remodeling is not limited to satisfy reparative and hypertrophic needs, but, through myocyte transcriptome/proteome renewal, it warrants the adaptations necessary to maintain tissue integrity. While vitamin D insufficiency promotes cell maladaptation, restoring vitamin D levels can correct/enhance the myogenic program. Hence, vitamin D fortified foods or supplementation potentially represents the desired approach to limit or avoid muscle wasting and ameliorate health. Nevertheless, consensus on protocols for vitamin D measurement and supplementation is still lacking, due to the high variability of lab tests and of the levels required in different contexts (i.e., age, sex, heath status, lifestyle). This review aims to describe how vitamin D can orchestrate skeletal muscle cell remodeling and myogenic programming, after reviewing the main processes and cell populations involved in this important process, whose correct progress highly impacts on human health. Topics on vitamin D optimal levels, supplementation and blood determination, which are still under debate, will be addressed.

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Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals

Cited by 66 publications

References 113 publications

LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway

LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway

Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs

Vitamin D Restores Skeletal Muscle Cell Remodeling and Myogenic Program: Potential Impact on Human Health

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