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. 2024 Sep 11:15:1392385.
doi: 10.3389/fphar.2024.1392385. eCollection 2024.

The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling

Dandan Zhang #  1   2   3 , Hao Cheng #  1 , Jing Wu  1 , Yaochuan Zhou  4 , Fei Tang  1 , Juan Liu  2 , Wuwen Feng  1   3 , Cheng Peng  1   3
Affiliations

The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling

Dandan Zhang et al. Front Pharmacol. .

Abstract

Introduction: As a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.

Methods: The effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.

Results: Rats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.

Conclusion: The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.

Keywords: aconite; antibiotic; bile acids; energy metabolism; fecal microbiota transplantation; gut microbiota.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
AA reduced body weight gain and enhanced the body temperature. (A) Experimental design and timeline. (B) Changes in body weight of rats. (C) Representative thermal images of rats. (D) Body temperature of rats before and after cold exposure. Data are presented as mean ± SD, n = 8. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 2
FIGURE 2
Effect of AA on BAT and WAT and the expression of UCP1. (A) Appearance and morphology of BAT and WAT. (B) Adipose tissue-to-body weight ratio. (C) Morphological changes in the BAT and WAT shown by HE staining (200×) and IHC staining of UCP1 in BAT (400×) and WAT (100×). (D) Quantifications of adipocyte sizes of WAT. (E, F) Quantitative analysis of UCP1 in WAT and BAT. Data are presented as mean ± SD, n = 8. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 3
FIGURE 3
Regulatory effects of AA on gut microbiota composition. (A) PCoA of gut microbiota based on OTU abundance. (B) NMDS of gut microbiota based on OTU abundance. (C) Main composition of gut bacteria at the phylum level. (D) Main composition of gut microbiota at the genus level. (E) Specific differences in bacteria between different groups at the genus level. (F) Cladogram analysis. (G) LEfSe analysis of the gut microbiota between three groups. Data are presented as mean ± SD, n = 6. *p < 0.05 and **p < 0.01.
FIGURE 4
FIGURE 4
Effect of AA on fecal BA metabolism. (A) Effect of AA on primary BAs. (B) Effect of AA on secondary BAs. (C) Effect of AA on the BA ratio. Data are presented as mean ± SD, n = 6. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 5
FIGURE 5
Pearson’s correlation analysis between fecal BAs and relative abundance of bacteria at the genus level. *p < 0.05, **p < 0.01, and ***p < 0.001. Red, positive correlation; blue, negative correlation.
FIGURE 6
FIGURE 6
AA promoted UCP1 expression via the regulation of BAs to upregulate the cAMP/PKA signaling pathway in BAT and WAT. (A, B) Protein expression of TGR5, PKA, and UCP1 in BAT and WAT detected by WB. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 7
FIGURE 7
Effect of AA on the metabolic phenotype in pseudo-germ-free rats. (A) Experimental design of the pseudo-germ-free experiment. (B) Body weight of each group of rats. (C) Representative thermal images of rats and body temperature of rats before and after cold exposure. (D) Adipose tissue morphology of BAT and WAT. (E) Adipose tissue-to-body weight ratio. (F) Morphological changes in the BAT and WAT shown by HE staining (200×) and IHC staining of UCP1 in the BAT (400×) and WAT (100×). (G) Quantifications of adipocyte sizes of WAT. (H, I) Expression of UCP1 in the BAT and WAT. Data are presented as mean ± SD, n = 8. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 8
FIGURE 8
Effects of FMT from AA on the body weight and body temperature in rats. (A) Experiment design of the FMT experiment. (B) Changes in the body weight of rats. (C) Representative thermal images of rats and body temperature of rats before and after cold exposure. Data are presented as mean ± SD, n = 8. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 9
FIGURE 9
Effects of FMT from AA on adipose tissues in rats. (A) Adipose tissue morphology of BAT and WAT. (B, C) Adipose tissue-to-body weight ratio. (D) Morphological changes in the BAT and WAT shown by HE staining (200×) and IHC staining of UCP1 in the BAT (400×) and WAT (100×). (E) Quantifications of adipocyte sizes of WAT. (F, G) Expression of UCP1 in the BAT and WAT. Data are presented as mean ± SD, n = 8. *p < 0.05 and ***p < 0.001.
FIGURE 10
FIGURE 10
Effect of FMT of AA on gut microbiota in rats. (A) PCoA of gut microbiota based on OTU abundance. (B) NMDS of gut microbiota based on OTU abundance. (C) Main composition of intestinal bacteria at the phylum level. (D) Main composition of gut microbiota at the genus level. (E) Specific differences in bacteria between different groups at the genus level. (F) Cladogram analysis. (G) LEfSe analysis of the gut microbiota between three groups. Data are presented as mean ± SD, n = 6. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 11
FIGURE 11
Effect of FMT of AA on fecal BA metabolism. (A) Effect of FMT of AA on primary BAs. (B) Effect of FMT of AA on secondary BAs. (C) Effect of FMT of AA on the BA ratio. Data are presented as mean ± SD, n = 6. *p < 0.05 and **p < 0.01.
FIGURE 12
FIGURE 12
Pearson’s correlation analysis between fecal BAs and relative abundance of bacteria at the genus level. *p < 0.05, **p < 0.01, and ***p < 0.001. Red, positive correlation; blue, negative correlation.
FIGURE 13
FIGURE 13
FMT of AA can also promote UCP1 expression via the regulation of BAs to upregulate the cAMP/PKA signaling pathway in BAT and WAT. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 14
FIGURE 14
Potential mechanism analysis of AA promoting energy metabolism along the gut microbiota–BA–adipose tissue axis.
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