The direct and indirect inhibition of proinflammatory adipose tissue macrophages by acarbose in diet-induced obesity

Xiaohui Li; Shimeng Zheng; Haozhe Xu; Zihan Zhang; Xiaotong Han; Yunxiong Wei; Hua Jin; Xiaonan Du; Hufeng Xu; Mengyi Li; Zhongtao Zhang; Songlin Wang; Guangyong Sun; Dong Zhang

doi:10.1016/j.xcrm.2024.101883

The direct and indirect inhibition of proinflammatory adipose tissue macrophages by acarbose in diet-induced obesity

Cell Rep Med. 2024 Dec 24:101883. doi: 10.1016/j.xcrm.2024.101883. Online ahead of print.

Authors

Xiaohui Li¹, Shimeng Zheng², Haozhe Xu², Zihan Zhang³, Xiaotong Han², Yunxiong Wei², Hua Jin³, Xiaonan Du³, Hufeng Xu³, Mengyi Li⁴, Zhongtao Zhang⁴, Songlin Wang⁵, Guangyong Sun⁶, Dong Zhang⁷

Affiliations

¹ Department of Endocrinology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
² Medical Research Center, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
³ Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
⁴ General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
⁵ Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Laboratory of Oral Health, Capital Medical University School of Basic Medicine, Beijing 100069, China.
⁶ Medical Research Center, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: [email protected].
⁷ Medical Research Center, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Laboratory of Oral Health, Capital Medical University School of Basic Medicine, Beijing 100069, China; Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing Friendship Hospital, Beijing 100050, China. Electronic address: [email protected].

PMID: 39742869
DOI: 10.1016/j.xcrm.2024.101883

Abstract

Inflammation is critical for obesity and obesity-induced insulin resistance (IR). In this study, we reveal the function and mechanism of acarbose on adipose tissue macrophage (ATM)-mediated inflammation in obesity and obesity-induced IR. First, acarbose enhances the abundance of propionic acid-producing Parasutterella, therefore indirectly inhibiting the survival and proinflammatory function of M1-like ATMs via GPR43. Most interestingly, acarbose can directly inhibit M1-like ATM-mediated inflammation through GPR120. Diet-induced obese mice exhibit nitrobenzoxadiazoles (NBD) fluorescence-labeled ATMs, but lean mice that also orally received NBD fluorescence-labeled acarbose do not exhibit NBD fluorescence-labeled ATMs. This direct inhibition of macrophages by acarbose is validated in mouse and human macrophages in vitro. In conclusion, our study reveals that acarbose directly and indirectly inhibits proinflammatory macrophage phenotype, which contributes to the improvement of obesity and obesity-induced IR. The understanding of the immune regulatory effects of acarbose may extend its potential for further therapeutic applications.

Keywords: Parasutterella excrementihominis; acarbose; adipose tissue macrophages; obesity; propionic acid.