DLK1 Is a Novel Link Between Reproduction and Metabolism

Imagem de Miniatura
Arquivos
art_GAMES_DLK1_Is_a_Novel_Link_Between_Reproduction_and_2019.PDF (887.71 KB)
Citações na Scopus
79
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ENDOCRINE SOC
Autores
LEES, Melissa
SPOUDEAS, Helen
DAUBER, Andrew
MACEDO, Delanie B.
Citação
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.104, n.6, p.2112-2120, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Delta-like homolog 1 (DLK1), also called preadipocyte factor 1, prevents adipocyte differentiation and has been considered a molecular gatekeeper of adipogenesis. A DLK1 complex genomic defect was identified in five women from a single family with central precocious puberty (CPP) and increased body fat percentage. Methods: We studied 60 female patients with a diagnosis of CPP or history of precocious menarche. Thirty-one of them reported a family history of precocious puberty. DLK1 DNA sequencing was performed in all patients. Serum DLK1 concentrations were measured using an ELISA assay in selected cases. Metabolic and reproductive profiles of adult women with CPP caused by DLK1 defects were compared with those of 20 women with idiopathic CPP. Results: We identified three frameshift mutations of DLK1 (p.Gly199Alafs*11, p.Va1271Cysfs*14, and p.Pro160Leufs*50) in five women from three families with CPP. Segregation analysis was consistent with the maternal imprinting of DLK1. Serum DLK1 concentrations were undetectable in three affected women. Metabolic abnormalities, such as overweight/obesity, early-onset glucose intolerance/type 2 diabetes mellitus, and hyperlipidemia, were more prevalent in women with the DLK1 mutation than in the idiopathic CPP group. Notably, the human metabolic alterations were similar to the previously described dlk1-null mice phenotype. Two sisters who carried the p.Gly199Alafs*11 mutation also exhibited polycystic ovary syndrome and infertility. Conclusions: Loss-of-function mutations of DLK1 are a definitive cause of familial CPP. The high prevalence of metabolic alterations in adult women who experienced CPP due to DLK1 defects suggests that this antiadipogenic factor represents a link between reproduction and metabolism.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/33128
Referências
  1. Abreu AP, 2013, NEW ENGL J MED, V368, P2467, DOI 10.1056/NEJMoa1302160
  2. Azziz R, 2016, NAT REV DIS PRIMERS, V2, DOI 10.1038/nrdp.2016.57
  3. Canoy D, 2015, CIRCULATION, V131, P237, DOI 10.1161/CIRCULATIONAHA.114.010070
  4. Carel JC, 2004, HUM REPROD UPDATE, V10, P135, DOI 10.1093/humupd/dmh012
  5. Carel JC, 2008, NEW ENGL J MED, V358, P2366, DOI 10.1056/NEJMcp0800459
  6. Dauber A, 2017, J CLIN ENDOCR METAB, V102, P1557, DOI 10.1210/jc.2016-3677
  7. Day FR, 2017, NAT GENET, V49, P834, DOI 10.1038/ng.3841
  8. de Bruin C, 2016, HORM RES PAEDIAT, V86, P342, DOI 10.1159/000446476
  9. Dewailly D, 2014, HUM REPROD UPDATE, V20, P334, DOI 10.1093/humupd/dmt061
  10. Elks CE, 2013, DIABETES CARE, V36, P3526, DOI 10.2337/dc13-0446
  11. Franceschi R, 2010, FERTIL STERIL, V93, P1185, DOI 10.1016/j.fertnstert.2008.11.016
  12. Guaraldi F, 2016, EUR J ENDOCRINOL, V174, pR79, DOI 10.1530/EJE-15-0590
  13. Ioannides Y, 2014, J MED GENET, V51, P495, DOI 10.1136/jmedgenet-2014-102396
  14. Kagami M, 2017, GENET MED, V19, P1356, DOI 10.1038/gim.2017.53
  15. Kopan R, 2009, CELL, V137, P216, DOI 10.1016/j.cell.2009.03.045
  16. Lazar L, 2014, CLIN ENDOCRINOL, V80, P570, DOI 10.1111/cen.12319
  17. Macedo DB, 2014, J CLIN ENDOCR METAB, V99, pE1097, DOI 10.1210/jc.2013-3126
  18. Moon YS, 2002, MOL CELL BIOL, V22, P5585, DOI 10.1128/MCB.22.15.5585-5592.2002
  19. Perry JRB, 2015, NAT REV ENDOCRINOL, V11, P725, DOI 10.1038/nrendo.2015.167
  20. Perry JRB, 2014, NATURE, V514, P92, DOI 10.1038/nature13545
  21. Prentice P, 2013, INT J OBESITY, V37, P1036, DOI 10.1038/ijo.2012.177
  22. Rhee M, 2016, SCI REP-UK, V6, DOI 10.1038/srep23960
  23. Simon D, 2016, EUR J ENDOCRINOL, V174, P1, DOI 10.1530/EJE-15-0488
  24. Smas CM, 1999, J BIOL CHEM, V274, P12632, DOI 10.1074/jbc.274.18.12632
  25. SMAS CM, 1993, CELL, V73, P725, DOI 10.1016/0092-8674(93)90252-L
  26. Solorzano CMB, 2012, STEROIDS, V77, P332, DOI 10.1016/j.steroids.2011.12.007
  27. Sul HS, 2009, MOL ENDOCRINOL, V23, P1717, DOI 10.1210/me.2009-0160
  28. TEMPLE IK, 1991, J MED GENET, V28, P511, DOI 10.1136/jmg.28.8.511
  29. Villanueva C, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0036134
  30. Won JC, 2016, MEDICINE, V95, DOI 10.1097/MD.0000000000003580

Coleções
Artigos e Materiais de Revistas Científicas - FM/MOG
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/25
Artigos e Materiais de Revistas Científicas - LIM/42
Artigos e Materiais de Revistas Científicas - LIM/58
Carregar mais