Xác định ký ức phiên mã của mô mỡ trong trường hợp chán ăn tâm thần

Molecular Medicine - Tập 29 - Trang 1-12 - 2023
Rizaldy C. Zapata1, Chanond A. Nasamran2, Daisy R. Chilin-Fuentes2, Stephanie C. Dulawa3, Olivia Osborn1
1Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, San Diego, USA
2Center for Computational Biology & Bioinformatics, School of Medicine, University of California San Diego, San Diego, USA
3Department of Psychiatry, School of Medicine, University of California San Diego, San Diego, USA

Tóm tắt

Chán ăn tâm thần (AN) là một bệnh lý phức tạp, gây suy nhược, được đặc trưng bởi nỗi sợ hãi mạnh mẽ về việc tăng cân và tập thể dục quá mức. Đây là rối loạn tâm thần gây tử vong cao nhất với tỷ lệ tái phát cao, tuy nhiên, sinh lý bệnh của nó vẫn chưa rõ ràng. Mô hình Chán ăn Dựa trên Hoạt động (ABA) là một mô hình chuột được công nhận rộng rãi về AN, tái hiện tình trạng ăn uống kém và hoạt động quá mức mặc dù trọng lượng cơ thể giảm, nhưng không thể hiện tính mãn tính. Ở đây, chúng tôi đã điều chỉnh mô hình ABA nguyên mẫu nhằm gia tăng thời gian để mất 25% trọng lượng cơ thể cơ bản từ ít hơn 7 ngày lên hơn 2 tuần. Chúng tôi đã sử dụng mô hình này để xác định các gen thay đổi kéo dài sau khi phục hồi cân nặng, đại diện cho một ký ức phiên mã về tình trạng thiếu dinh dưỡng và có thể góp phần vào việc tái phát của AN thông qua phân tích giải trình tự RNA. Chúng tôi tập trung vào mô mỡ vì nó được xác định là vị trí chính của ký ức phiên mã về tình trạng thừa dinh dưỡng. Chúng tôi đã xác định được 300 gen rối loạn điều hòa không hồi phục sau khi phục hồi cân nặng sau ABA, bao gồm Calm2 và Vps13d, những gen này có thể là các yếu tố điều hòa toàn cầu của ký ức phiên mã trong cả tình trạng thừa và thiếu dinh dưỡng mãn tính. Chúng tôi đã chứng minh sự tồn tại của các thay đổi kéo dài trong phiên mã mô mỡ ở chuột ABA sau khi phục hồi cân nặng. Mặc dù nằm ở phổ đối diện của sự rối loạn về trọng lượng, phần lớn các gen ký ức phiên mã của tình trạng thiếu và thừa dinh dưỡng không trùng lặp, cho thấy các cơ chế khác nhau tham gia trong những trạng thái dinh dưỡng cực đoan này.

Từ khóa

#Chán ăn tâm thần #mô mỡ #ký ức phiên mã #gen rối loạn #phục hồi cân nặng #RNA sequencing

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