Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis

Hilgendorf, Keren I.; Johnson, Carl T.; Mezger, Anja; Rice, Sarah E.; Norris, Alessandra M.; Demeter, János; Greenleaf, William J.; Reiter, Jeremy F.; Kopinke, Daniel; Jackson, Peter K.

doi:10.1016/j.cell.2019.11.005

Cited by 193 publications

(178 citation statements)

References 94 publications

(92 reference statements)

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“…Consistently, reanalysis of data generated from previous studies in human and mouse reveals that PDGFD expression is enriched in preadipocytes and is decreased during the adipogenesis from precursor cells (Fig. 4E-F) [22,23]. These observations strongly suggest that PDGFD plays a critical role in the initiation and/or commitment of preadipocytes and this function is conserved and universal across species.…”

Section: Discussionsupporting

confidence: 83%

“…PDGFD expression in adipose tissues/cells in mouse and human Micro-array data of different cell types isolated from human white adipose tissues by uorescenceactivated cell sorting (FACS) including CD45-/CD34+/CD31-(progenitors), CD45+/CD14+/CD206+ (total macrophages), CD45+/CD14+CD206+/CD11c+ (M1 macrophages), CD45+/CD14+/CD206+/CD11c-(M2 macrophages), CD45+/CD3+ (Total T cells), CD45+/CD3+/CD4+/CD8-(Th T-cells), CD45+/CD3+/CD4-/CD8+ (Tc T-cells) (GSE100795) [23] were obtained from GEO database and reanalyzed with online build-in tool GEO2R. Raw gene count matrix generated from RNA-seq for mouse 3T3-L1 preadiopocytes and differentiating cells at 24 hours after induction by DHA differentiation cocktail was obtained from GEO database (GSE118471) [22]. FPKM was calculated for each sample and used for quanti cation of gene expression level.…”

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confidence: 99%

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Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Dong

Yang

Han

et al. 2020

Preprint

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Background: Fat tail is a unique trait in sheep acquired during domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures. Results: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistical tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological and gene expression analyses demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Further retrospective analysis of public transcriptomic datasets revealed that PDGFD expression is down-regulated during adipogenesis in both human and mouse, and is higher in fat tissues of obese individuals than that in lean individuals. Conclusions: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the selection of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases.

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Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 99%

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Dong

Yang

Han

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Consistently, reanalysis of data generated from previous studies in human and mouse reveals that PDGFD expression is enriched in preadipocytes and is decreased during the adipogenesis from precursor cells (Fig. 4E-F) [23,24]. These observations strongly suggest that PDGFD plays a critical in the initiation and/or commitment of preadipocytes and this function is conserved and universe across species.…”

Section: Discussionsupporting

confidence: 83%

“…PDGFD expression in adipose tissues/cells in mouse and human Micro-array data of different cell types isolated from human white adipose tissues by uorescenceactivated cell sorting (FACS) including CD45-/CD34+/CD31-(progenitors), CD45+/CD14+/CD206+ (total macrophages), CD45+/CD14+CD206+/CD11c+ (M1 macrophages), CD45+/CD14+/CD206+/CD11c-(M2 macrophages), CD45+/CD3+ (Total T cells), CD45+/CD3+/CD4+/CD8-(Th T-cells), CD45+/CD3+/CD4-/CD8+ (Tc T-cells) (GSE100795) [24] were obtained from GEO database and reanalyzed with online build-in tool GEO2R. Raw gene count matrix generated from RNA-seq for mouse 3T3-L1 preadiopocytes and differentiating cells at 24 hours after induction by DHA differentiation cocktail was obtained from GEO database (GSE118471) [23]. FPKM was calculated for each sample and used for quanti cation of gene expression level.…”

Section: Rna-sequencing and Bioinformatics Analysismentioning

confidence: 99%

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Dong

Yang

Han

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Fat tail is a special trait in sheep acquired during sheep domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures. Results: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistic tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Further analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological analysis and gene expression analysis demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Luciferase reporter assays showed that a segment of conserved sequence surrounding the orthologous site of one mutation found in sheep is functional in regulating PDGFD expression. Conclusions: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the evolution of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases.

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“…Interestingly, ciliated preadipocytes preferentially populate the perivascular areas of WAT and initiate adipogenesis when the individual is on a high‐fat diet. In this context, Hilgendorf et al hypothesized that preadipocytes use their cilia to sense mediators in the blood stream and regulate adipogenesis. By a series of elegant experiments using animals and in vitro models, they show that the cilia determine the adipogenic potential of preadipocytes and that these organelles are lost during adipocyte maturation.…”

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confidence: 99%

Omega‐3 fatty acids and the regulation of adipogenesis

Eguiluz‐Gracia

Bogas

2020

Allergy

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Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis

Cited by 193 publications

References 94 publications

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Omega‐3 fatty acids and the regulation of adipogenesis

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Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis

Cited by 193 publications

References 94 publications

­­­­­­Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

­­­­­­Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

­­­­­­Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Omega‐3 fatty acids and the regulation of adipogenesis

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Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep