신성재 (연세대학교 의과대학)

한빛사논문

조회242

연세대학교 의과대학

EBioMedicine, Available online 17 June 2024 | https://doi.org/10.1016/j.ebiom.2024.105198 Protein-energy restriction-induced lipid metabolism disruption causes stable-to-progressive disease shift in Mycobacterium avium-infected female mice

Sangwon Choi,^a Ju Mi Lee,^a Keu Eun San Kim,^a Ji-Hae Park,^a Lee-Han Kim,^a Jiyun Park,^a Yaerin Jeon,^a Byung Woo Jhun,^b Su-Young Kim,^b Jung Joo Hong,^c,d and Sung Jae Shin^a,∗

^aDepartment of Microbiology, Institute for Immunology and Immunological Disease, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, South Korea

^bDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea

^cNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, 28116, South Korea

^dKRIBB School of Bioscience, Korea University of Science & Technology (UST), Daejeon, 34113, South Korea

^*Corresponding author : Sung Jae Shin

Abstract

Background

Disease susceptibility and progression of Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with multiple factors, including low body mass index (BMI). However, the specific impact of low BMI on MAC-PD progression remains poorly understood. This study aims to examine the progression of MAC-PD in the context of low BMI, utilising a disease-resistant mouse model.

Methods

We employed a MAC infection-resistant female A/J mouse model to compare the progression of MAC-PD under two dietary conditions: one group was fed a standard protein diet, representing protein-energy unrestricted conditions, and the other was fed a low protein diet (LPD), representing protein-energy restriction.

Findings

Our results reveal that protein-energy restriction significantly exacerbates MAC-PD progression by disrupting lipid metabolism. Mice fed an LPD showed elevated fatty acid levels and related gene expressions in lung tissues, similar to findings of increased fatty acids in the serum of patients who exhibited the MAC-PD progression. These mice also exhibited increased CD36 expression and lipid accumulation in macrophages upon MAC infection. In vitro experiments emphasised the crucial role of CD36-mediated palmitic acid uptake in bacterial proliferation. Importantly, in vivo studies demonstrated that administering anti-CD36 antibody to LPD-fed A/J mice reduced macrophage lipid accumulation and impeded bacterial growth, resulting in remarkable slowing disease progression.

Interpretation

Our findings indicate that the metabolic status of host immune cells critically influences MAC-PD progression. This study highlights the potential of adequate nutrient intake in preventing MAC-PD progression, suggesting that targeting CD36-mediated pathways might be a host-directed therapeutic strategy to managing MAC infection.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-19)
연구진국내 연구진
분야 생명과학 > 미생물학

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