Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion

Chun-Guang Guo; Rui Sun; Xiao Wang; Ye Yuan; Yan Xu; Shihan Li; Xueting Sun; Jue Wang; Xinli Hu; Tiannan Guo; Xiao-Wei Chen; Rui-Ping Xiao; Xiuqin Zhang

Molecular Metabolism (Jan 2024)

Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion

Chun-Guang Guo,
Rui Sun,
Xiao Wang,
Ye Yuan,
Yan Xu,
Shihan Li,
Xueting Sun,
Jue Wang,
Xinli Hu,
Tiannan Guo,
Xiao-Wei Chen,
Rui-Ping Xiao,
Xiuqin Zhang

Affiliations

Chun-Guang Guo: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Rui Sun: Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, China
Xiao Wang: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Ye Yuan: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Yan Xu: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Shihan Li: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Xueting Sun: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Jue Wang: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Xinli Hu: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
Tiannan Guo: Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, China
Xiao-Wei Chen: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Corresponding author. Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.
Rui-Ping Xiao: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Corresponding author. Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.
Xiuqin Zhang: Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; Corresponding author. Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.

Journal volume & issue: Vol. 79
p. 101847

Abstract

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Objective: Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption. Methods: We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models. Results: We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins. Conclusions: SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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