Lactoferrin bò thúc đẩy tiêu hao năng lượng thông qua con đường tín hiệu cAMP-PKA ở tế bào mỡ nâu tái lập trình của người

Biology of Metals - Tập 31 - Trang 415-424 - 2018
Kanae Nakamura1, Tsunao Kishida2, Akika Ejima3, Riho Tateyama1, Satoru Morishita1,4, Tomoji Ono1,5, Michiaki Murakoshi1,5,6, Keikichi Sugiyama7, Hoyoku Nishino6, Osam Mazda2
1Research and Development Headquarters, Lion Corporation, Odawara, Japan
2Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan
3Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
4“Food for Life”, Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan
5Advanced Medical Research Center, Yokohama City University, Yokohama, Japan
6Kyoto Prefectural University of Medicine, Kyoto, Japan
7Research Organization of Science and Engineering, Ritsumeikan University, Kusatsu, Japan

Tóm tắt

Lactoferrin (LF) là một protein đa chức năng có trong sữa động vật có vú. Chúng tôi đã báo cáo trước đây rằng LF bò được bao bọc bằng ruột đã giảm mỡ nội tạng trong một nghiên cứu lâm sàng mù đôi. Chúng tôi đã chứng minh thêm rằng LF bò (bLF) ức chế quá trình hình thành tế bào mỡ và thúc đẩy phân hủy lipid trong các tế bào adipocyte trắng, nhưng tác động của bLF đối với các tế bào adipocyte nâu vẫn chưa được làm sáng tỏ. Trong nghiên cứu này, chúng tôi đã điều tra tác động của bLF đến tiêu hao năng lượng và con đường tín hiệu cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) bằng cách sử dụng các tế bào adipocyte nâu tái lập trình của người được tạo ra bởi truyền gen. bLF với nồng độ ≥ 100 μg/mL đã làm tăng đáng kể mức mRNA của protein không tách biệt 1 (UCP1), với giá trị tối đa được quan sát 4 giờ sau khi thêm bLF. Ở cùng thời điểm đó, sự kích thích bLF cũng đã làm tăng đáng kể mức tiêu thụ oxy. Phân tích con đường tín hiệu cho thấy sự gia tăng nhanh chóng của cAMP nội bào và mức độ phosphoryl hóa protein liên kết yếu tố phản ứng cAMP (CREB) bắt đầu 5 phút sau khi thêm bLF. Mức mRNA của thụ thể gamma ức chế tăng sinh peroxisome 1-alpha (PGC1α) cũng đã tăng đáng kể sau 1 giờ kích thích bằng bLF. H-89, một chất ức chế PKA đặc hiệu, đã làm mất tác dụng biểu hiện gen UCP1 do bLF gây ra. Hơn nữa, protein liên kết thụ thể (Rap), một đối kháng của protein liên quan thụ thể lipoprotein có mật độ thấp 1 (LRP1), đã làm giảm đáng kể biểu hiện gen UCP1 do bLF gây ra theo cách phụ thuộc vào liều lượng. Những kết quả này gợi ý rằng bLF thúc đẩy biểu hiện gen UCP1 ở các tế bào adipocyte nâu thông qua con đường tín hiệu cAMP-PKA qua thụ thể LRP1, dẫn đến tăng tiêu hao năng lượng.

Từ khóa

#Lactoferrin #protein không tách biệt 1 #tế bào mỡ nâu #tín hiệu cAMP-PKA #tiêu hao năng lượng.

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