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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.755598/full |
| _version_ | 1818833464936366080 |
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| author | Yan Xiong Yan Xiong Yan Xiong Yuxue Wang Qing Xu Qing Xu An Li Yongqi Yue Yan Ma Yaqiu Lin Yaqiu Lin Yaqiu Lin |
| author_facet | Yan Xiong Yan Xiong Yan Xiong Yuxue Wang Qing Xu Qing Xu An Li Yongqi Yue Yan Ma Yaqiu Lin Yaqiu Lin Yaqiu Lin |
| author_sort | Yan Xiong |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T02:19:21Z |
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| id | doaj.art-f42ca9c4738b4cbbb70366a2da0e5b8c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T02:19:21Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-f42ca9c4738b4cbbb70366a2da0e5b8c2022-12-21T20:40:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-10-011210.3389/fphys.2021.755598755598LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion PathwayYan Xiong0Yan Xiong1Yan Xiong2Yuxue Wang3Qing Xu4Qing Xu5An Li6Yongqi Yue7Yan Ma8Yaqiu Lin9Yaqiu Lin10Yaqiu Lin11Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province, Southwest Minzu University, Chengdu, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaState Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province, Southwest Minzu University, Chengdu, ChinaCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, ChinaIntramuscular 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.755598/fullIMFintramuscular adipocyteadipogenesisLKB1focal adhesion pathwayFAK |
| spellingShingle | Yan Xiong Yan Xiong Yan Xiong Yuxue Wang Qing Xu Qing Xu An Li Yongqi Yue Yan Ma Yaqiu Lin Yaqiu Lin Yaqiu Lin LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway Frontiers in Physiology IMF intramuscular adipocyte adipogenesis LKB1 focal adhesion pathway FAK |
| 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 | IMF intramuscular adipocyte adipogenesis LKB1 focal adhesion pathway FAK |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.755598/full |
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