Chữ ký metyl hóa DNA trong máu phản ánh sự giảm cân thành công trong các can thiệp lối sống: thử nghiệm CENTRAL

Springer Science and Business Media LLC - Tập 12 - Trang 1-18 - 2020
Maria Keller1,2,3, Anat Yaskolka Meir4, Stephan H. Bernhart5,6,7, Yftach Gepner4,8, Ilan Shelef9, Dan Schwarzfuchs10,11, Gal Tsaban4, Hila Zelicha4, Lydia Hopp5, Luise Müller2,3, Kerstin Rohde1,2, Yvonne Böttcher3,12,13, Peter F. Stadler6,14,15,16,17,18,19, Michael Stumvoll1,2,3,20, Matthias Blüher1,2, Peter Kovacs2, Iris Shai4
1Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany
2Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
3IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany
4Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
5Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany
6Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany
7Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
8Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute, Tel Aviv University, Ramat Aviv, Israel
9Soroka University Medical Center, Beer-Sheva, Israel
10Soroka University Medical Center, Beer Sheva, Israel
11Nuclear Research Center-Negev, Dimona, Israel
12Department of Clinical Molecular Biology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
13Medical Division, Akershus University Hospital, Lørenskog, Norway
14Competence Center for Scalable Data Services and Solutions Dresden/Leipzig, German Centre for Integrative Biodiversity Research (iDiv), and Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
15Max Planck Institute for Mathematics in the Sciences, Leipzig, Germany
16Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
17Department of Theoretical Chemistry, University of Vienna, Vienna, Austria
18Center for RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark
19Santa Fe Institute, Santa Fe, USA
20Deutsches Zentrum für Diabetesforschung, Helmholtz Zentrum München, Neuherberg, USA

Tóm tắt

Một trong những thách thức lớn trong điều trị béo phì là giải thích sự khác biệt cao trong phản ứng của từng cá nhân đối với các can thiệp về chế độ ăn uống và hoạt động thể chất. Trong nghiên cứu này, chúng tôi đã kiểm tra giả thuyết rằng những thay đổi metyl hóa DNA cụ thể phản ánh khả năng phản ứng của từng cá nhân đối với can thiệp lối sống và có thể đóng vai trò là các yếu tố dự đoán epigenetic cho việc giảm cân thành công. Chúng tôi tiến hành phân tích metyl hóa DNA trên toàn genome trong các mẫu máu từ 120 đối tượng (90% là nam, độ tuổi trung bình ± SD = 49 ± 9 năm, chỉ số khối cơ thể (BMI) = 30.2 ± 3.3 kg/m2) tham gia thử nghiệm ngẫu nhiên có kiểm soát CENTRAL kéo dài 18 tháng, những người đã thực hiện chế độ ăn Địa Trung Hải/ít carbohydrate hoặc chế độ ăn ít chất béo với hoặc không có hoạt động thể chất. Phân tích so sánh các đối tượng nam có sự giảm cân rõ rệt nhất (những người phản ứng, thay đổi trọng lượng trung bình − 16%) so với những người không phản ứng (+ 2.4%) (N = 10 mỗi nhóm) cho thấy sự khác biệt đáng kể trong metyl hóa DNA của một số gen bao gồm LRRC27, CRISP2, và SLFN12 (tất cả điều chỉnh P < 1 × 10−5). Phân tích chức năng gene cho thấy rằng các quá trình sinh học như bám dính tế bào và các chức năng phân tử như liên kết ion canxi có thể đóng vai trò quan trọng trong việc xác định sự thành công của các liệu pháp can thiệp trong điều trị béo phì. Sự liên kết giữa toàn bộ epigenome với giảm cân tương đối (%) đã xác định 15 CpG có tương quan âm với thay đổi trọng lượng sau can thiệp (tất cả P kết hợp < 1 × 10− 4) bao gồm những đối tượng béo phì mới và đã biết như NUDT3 và NCOR2. Điểm số metyl hóa DNA cơ bản dự đoán tốt hơn sự giảm cân thành công [diện tích dưới đường cong (AUC) của đặc điểm hoạt động nhận (ROC) = 0.95–1.0] so với các yếu tố dự đoán như tuổi và BMI (AUC ROC = 0.56). Sự giảm cân cơ thể sau can thiệp lối sống 18 tháng có liên quan đến các chữ ký metyl hóa cụ thể. Hơn nữa, sự khác biệt metyl hóa trong các gen đã xác định có thể phục vụ như biomarker tiên lượng để dự đoán liệu pháp giảm cân thành công và do đó góp phần vào sự tiến bộ trong điều trị béo phì tùy chỉnh cho bệnh nhân.

Từ khóa

#DNA methylation #weight loss #obesity treatment #lifestyle intervention #epigenetic predictors

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