1. Academic Validation
  2. Limosilactobacillus reuteri and caffeoylquinic acid synergistically promote adipose browning and ameliorate obesity-associated disorders

Limosilactobacillus reuteri and caffeoylquinic acid synergistically promote adipose browning and ameliorate obesity-associated disorders

  • Microbiome. 2022 Dec 15;10(1):226. doi: 10.1186/s40168-022-01430-9.
Yameng Liu # 1 Xianchun Zhong # 1 2 Suqin Lin # 3 Hualing Xu 3 Xinyu Liang 3 Yibin Wang 1 4 Jingyi Xu 3 Kanglong Wang 1 Xiaozhen Guo 1 Jiawen Wang 5 Minjun Yu 1 4 Cuina Li 1 Cen Xie 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China.
  • 2 School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China.
  • 3 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
  • 4 University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
  • 5 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, People's Republic of China.
  • 6 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China. [email protected].
  • 7 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. [email protected].
  • 8 University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China. [email protected].
  • # Contributed equally.
Abstract

Objective: High intake of caffeoylquinic acid (CQA)-rich dietary supplements, such as green coffee bean extracts, offers health-promoting effects on maintaining metabolic homeostasis. Similar to many active herbal ingredients with high pharmacological activities but low bioavailability, CQA has been reported as a promising thermogenic agent with anti-obesity properties, which contrasts with its poor oral absorption. Intestinal tract is the first site of CQA exposure and gut microbes might react quickly to CQA. Thus, it is of interest to explore the role of gut microbiome and microbial metabolites in the beneficial effects of CQA on obesity-related disorders.

Results: Oral CQA supplementation effectively enhanced energy expenditure by activating browning of adipose and thus ameliorated obesity-related metabolic dysfunctions in high fat diet-induced obese (DIO) mice. Here, 16S rRNA gene amplicon sequencing revealed that CQA treatment remodeled the gut microbiota to promote its anti-obesity actions, as confirmed by Antibiotic treatment and fecal microbiota transplantation. CQA enriched the gut commensal species Limosilactobacillus reuteri (L. reuteri) and stimulated the production of short-chain fatty acids, especially propionate. Mono-colonization of L. reuteri or low-dose CQA treatment did not reduce adiposity in DIO mice, while their combination elicited an enhanced thermogenic response, indicating the synergistic effects of CQA and L. reuteri on obesity. Exogenous propionate supplementation mimicked the anti-obesity effects of CQA alone or when combined with L. reuteri, which was ablated by the Monocarboxylate Transporter (MCT) inhibitor 7ACC1 or MCT1 disruption in inguinal white adipose tissues to block propionate transport.

Conclusions: Our data demonstrate a functional axis among L. reuteri, propionate, and beige fat tissue in the anti-obesity action of CQA through the regulation of thermogenesis. These findings provide mechanistic insights into the therapeutic use of herbal ingredients with poor bioavailability via their interaction with the gut microbiota. Video Abstract.

Keywords

Browning; Obesity; Prebiotic; Probiotics; Propionate; Short-chain fatty acids; Thermogenesis.

Figures
Products