Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue

Petrus, Paul; Mejhert, Niklas; Corrales, Patricia; Lecoutre, Simon; Li, Qian; Maldonado, Estela; Kulyté, Agné; López, Yamila; Campbell, Mark; Acosta, Juan R.; Laurencikiene, Jurga; Douagi, Iyadh; Gao, Hui; Martı́nez-Álvarez, Concepción; Hedén, Per; Spalding, Kirsty L.; Vidal-Puig, António; Medina-Gómez, Gema; Arner, Peter

doi:10.1016/j.celrep.2018.09.069

Cited by 86 publications

(98 citation statements)

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“…More interestingly, this expression pattern holds true in mouse and human, with obese individuals exhibiting higher level of PDGFD expression in adipose tissues ( Fig. 4C-E) [23,24]. Together with a recent study reporting that PDGFD expression is associated with adipocyte number in human white adipose tissue [37], we propose that PDGFD is a novel regulator of adipogenesis and adipocyte hemostasis. Further gain/lossof-function assays are necessary to confirm this potential function.…”

Section: Discussionsupporting

confidence: 80%

Genomic analysis of worldwide sheep breeds revealsPDGFDa major target of fat-tail selection in sheep

Dong

Yang

Han

et al. 2020

Preprint

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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. 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 (F ST ) 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 sheep mutation is functional in regulating PDGFD expression in human. 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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Section: Discussionsupporting

confidence: 80%

Genomic analysis of worldwide sheep breeds revealsPDGFDa major target of fat-tail selection in sheep

Dong

Yang

Han

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…4J-K) [27,28]. Together with a recent study reporting that PDGFD is expression is associated with adipocyte number in human white adipose tissue [29], we propose that PDGFD is a novel regulator of adipogenesis and adipocyte hemostasis. Further gain/loss-of-function assays are necessary to con rm this potential function.…”

Section: Discussionsupporting

confidence: 70%

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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“…impaired adipogenesis. The transcription factor early B-cell factor 1 (EBF1) has been shown to correlate with adipose morphology, with decreased expression and activity in hypertrophy 88 , and transforming growth factor-beta 3 has recently been shown to regulate subcutaneous adipocyte number 89 .…”

Section: Adipocyte Size and Numbermentioning

confidence: 99%

Body fat mass and distribution as predictors of metabolic outcome and weight loss after Roux-en-Y gastric bypass

Hogling

Rydén

Bäckdahl

et al. 2018

Surgery for Obesity and Related Diseases

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Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue

Cited by 86 publications

References 50 publications

Genomic analysis of worldwide sheep breeds revealsPDGFDa major target of fat-tail selection in sheep

Genomic analysis of worldwide sheep breeds revealsPDGFDa 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

Body fat mass and distribution as predictors of metabolic outcome and weight loss after Roux-en-Y gastric bypass

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Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue

Cited by 86 publications

References 50 publications

Genomic analysis of worldwide sheep breeds revealsPDGFDa major target of fat-tail selection in sheep

Genomic analysis of worldwide sheep breeds revealsPDGFDa 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

Body fat mass and distribution as predictors of metabolic outcome and weight loss after Roux-en-Y gastric bypass

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