Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Các tác động đặc hiệu của đồng phân CLA lên biểu hiện gen trong mô mỡ của người phụ thuộc vào đa hình PPARγ2 P12A: một nghiên cứu ngẫu nhiên, mù đôi, đối chứng với thiết kế chéo
Tóm tắt
Receptor PPARγ (Peroxisome proliferator-activated receptor gamma) là một điều hòa chính trong mô mỡ. Biến thể hiếm Pro12Ala của PPARγ2 có liên quan đến việc giảm nguy cơ kháng insulin. Là những hợp chất liên kết với PPARγ trong chế độ ăn uống, axit linoleic liên hợp (CLA) đã thu hút sự chú ý đáng kể do những tác động của chúng lên thành phần cơ thể, ung thư, xơ vữa động mạch, tiểu đường, béo phì và viêm, mặc dù một số tác động chỉ được chứng minh trong các thử nghiệm trên động vật và kết quả trong các nghiên cứu trên người không phải lúc nào cũng nhất quán. Trong nghiên cứu hiện tại, chúng tôi đã điều tra tác động của việc bổ sung CLA lên biểu hiện gen toàn bộ genome trong các mẫu sinh thiết mô mỡ từ 11 người mang gen Ala12Ala và 23 người mang gen Pro12Pro. Các đối tượng đã trải qua bốn giai đoạn can thiệp (4 tuần) theo thiết kế ngẫu nhiên mù đôi với sự nhận được 4,25g/ngày của hoặc là cis-9, trans-11 CLA, trans-10,cis-12 CLA, hỗn hợp 1:1 của cả hai đồng phân hoặc một chế phẩm dầu axit linoleic tham chiếu. Sau mỗi giai đoạn can thiệp, các mẫu sinh thiết đã được lấy, và các phương pháp vi mạch biểu hiện toàn bộ genome được áp dụng, đồng thời các gen quan tâm được xác thực bằng PCR thời gian thực. Các gen tham gia chuyển hóa lipid sau đây đã được điều chỉnh bởi CLA: LDLR, FASN, SCD, FADS1 và UCP2 đã được kích thích, trong khi ABCA1, CD36 và CA3 bị ức chế. Các yếu tố phiên mã PPARγ, NFAT5, CREB5 và EBF1, adipokine NAMPT, các thành viên của chuỗi tín hiệu insulin SORBS1 và IGF1 và IL6ST cũng đã bị ức chế, trong khi adipokine THBS1 và GLUT4 liên quan đến tín hiệu insulin thì được kích thích. So với trans-10,cis-12 CLA và hỗn hợp CLA, đồng phân cis-9, trans-11 CLA gây ra tác động yếu hơn. Chỉ có CD36 (-1.2 lần) và THBS1 (1.5 lần) được điều chỉnh. Tác động của CLA lên biểu hiện gen PPARγ và leptin phụ thuộc vào kiểu gen PPARγ2. Dữ liệu cho thấy tác động cụ thể của đồng phân CLA lên chuyển hóa glucose và lipid phụ thuộc vào kiểu gen và ít nhất một phần được điều hòa bởi PPARγ.
Từ khóa
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