한빛사논문
- 조회354
서울대학교병원
Han-Mo Yang1,2,3†, Joonoh Kim2,3†, Baek-Kyung Kim2,3†, Hyun Ju Seo2,3, Ju-Young Kim2,3, Joo-Eun Lee2,3, Jaewon Lee2,3, Jihye You2,3, Sooryeonhwa Jin2,3, Yoo-Wook Kwon2,3, Hyun-Duk Jang2,3, and Hyo-Soo Kim1,2,3,4*
1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
2National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea.
3Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
4Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, 03080, Korea.
†These authors contributed equally to this work.
*Address correspondence to: Hyo-Soo Kim
Abstract
Resistin plays an important role in the pathophysiology of obesity-mediated insulin resistance in mice. However, the biology of resistin in humans is quite different from that in rodents. Therefore, the association between resistin and insulin resistance remains unclear in humans. Here, we tested whether and how the endocannabinoid system (ECS) control circulating peripheral blood mononuclear cells (PBMCs) that produce resistin and infiltrate into the adipose tissue, heart, skeletal muscle, and liver, resulting in inflammation and insulin resistance. Using human PBMCs, we investigate whether the ECS is connected to human resistin. To test whether the ECS regulates inflammation and insulin resistance in vivo, we used 2 animal models such as “humanized” nonobese diabetic/Shi-severe combined immunodeficient interleukin-2Rγ (null) (NOG) mice and “humanized” resistin mouse models, which mimic human body. In human atheromatous plaques, cannabinoid 1 receptor (CB1R)-positive macrophage was colocalized with the resistin expression. In addition, resistin was exclusively expressed in the sorted CB1R-positive cells from human PBMCs. In CB1R-positive cells, endocannabinoid ligands induced resistin expression via the p38–Sp1 pathway. In both mouse models, a high-fat diet increased the accumulation of endocannabinoid ligands in adipose tissue, which recruited the CB1R-positive cells that secrete resistin, leading to adipose tissue inflammation and insulin resistance. This phenomenon was suppressed by CB1R blockade or in resistin knockout mice. Interestingly, this process was accompanied by mitochondrial change that was induced by resistin treatment. These results provide important insights into the ECS–resistin axis, leading to the development of metabolic diseases. Therefore, the regulation of resistin via the CB1R could be a potential therapeutic strategy for cardiometabolic diseases.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-04)
- 국내 연구진
- 생명과학 > 세포생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
