The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition.

Autor:	Lee K; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Vakili S; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Burden HJ; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Adams S; Discipline of Nutrition, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Smith GC; Department of Pharmacology, School of Medical Sciences, UNSW Australia, Kensington, Australia., Kulatea B; Discipline of Nutrition, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Wright-McNaughton M; Department of Medicine, University of Otago Wellington, Wellington, New Zealand., Sword D; Department of Medicine, University of Otago Wellington, Wellington, New Zealand., Watene-O'Sullivan C; Moko Foundation and Waharoa Ki Te Toi Research Centre, Kaitaia, New Zealand., Atiola RD; Discipline of Nutrition, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Paul RG; Waikato Medical Research Centre, University of Waikato, Hamilton, New Zealand., Plank LD; Department of Surgery, School of Medicine, The University of Auckland, Auckland, New Zealand., Kallingappa P; Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand., King F; Ngati Porou Hauora, Te Puia Springs, New Zealand., Wilcox P; Department of Mathematics and Statistics, University of Otago, New Zealand., Merriman TR; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Biochemistry, School of Biomedical Sciences, University of Otago, New Zealand; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Alabama, United States., Krebs JD; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Medicine, University of Otago Wellington, Wellington, New Zealand., Hall RM; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Medicine, University of Otago Wellington, Wellington, New Zealand., Murphy R; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand., Merry TL; Discipline of Nutrition, School of Medical Sciences, The University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand., Shepherd PR; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand; Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand. Electronic address: peter.shepherd@auckland.ac.nz.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2022 May; Vol. 59, pp. 101464. Date of Electronic Publication: 2022 Feb 24.
DOI:	10.1016/j.molmet.2022.101464
Abstrakt:	Objective: The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Māori and peoples of Polynesia), with a frequency of up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It remains unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. Methods: We undertook body composition analysis using DXA in 189 young men of Māori and Pacific descent living in Aotearoa New Zealand. Further investigation was carried out in two orthologous Arg458Gln knockin mouse models on FVB/NJ and C57BL/6j backgrounds. Results: The rs373863828 A allele was associated with lower fat mass when adjusted for BMI (p < 0.05) and was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p < 0.05). Supporting the human data, significant reductions in adipose tissue mass were observed in the knockin mice. This was more significant in older mice in both backgrounds and appeared to be the result of reduced age-associated increases in fat mass. The older male knockin mice on C57BL/6j background also had increased grip strength (p < 0.01) and lower levels of myostatin (p < 0.05). Conclusion: Overall, these results prove that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contribute to an age-dependent lowering of fat mass, at least in males. (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu