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LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway
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 repo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548615/ https://www.ncbi.nlm.nih.gov/pubmed/34721078 http://dx.doi.org/10.3389/fphys.2021.755598 |
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author | Xiong, Yan Wang, Yuxue Xu, Qing Li, An Yue, Yongqi Ma, Yan Lin, Yaqiu |
author_facet | Xiong, Yan Wang, Yuxue Xu, Qing Li, An Yue, Yongqi Ma, Yan Lin, Yaqiu |
author_sort | Xiong, Yan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8548615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85486152021-10-28 LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway Xiong, Yan Wang, Yuxue Xu, Qing Li, An Yue, Yongqi Ma, Yan Lin, Yaqiu Front Physiol Physiology 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. Frontiers Media S.A. 2021-10-13 /pmc/articles/PMC8548615/ /pubmed/34721078 http://dx.doi.org/10.3389/fphys.2021.755598 Text en Copyright © 2021 Xiong, Wang, Xu, Li, Yue, Ma and Lin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Xiong, Yan Wang, Yuxue Xu, Qing Li, An Yue, Yongqi Ma, Yan Lin, Yaqiu LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway |
title | LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway |
title_full | LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway |
title_fullStr | LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway |
title_full_unstemmed | LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway |
title_short | LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway |
title_sort | lkb1 regulates goat intramuscular adipogenesis through focal adhesion pathway |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548615/ https://www.ncbi.nlm.nih.gov/pubmed/34721078 http://dx.doi.org/10.3389/fphys.2021.755598 |
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