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. 2025 Mar 18;20(1):20251152.
doi: 10.1515/med-2025-1152. eCollection 2025.

A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue

Affiliations

A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue

Naomi Osakabe et al. Open Med (Wars). .

Abstract

Introduction: Flavan-3-ols (FLs), astringent polyphenols, are known to have low bioavailability and induce excessive sympathetic nervous system activation. This study aimed to compare the effects of FLs on brown, subcutaneous, and visceral adipose tissue in mice.

Methods: C57BL/6J male mice fed a standard or high-fat diet were given water or 50 mg/kg FL orally by gavage for 2 weeks. Excised brown, inguinal, and epididymal fat tissues were prepared for frozen sectioning. After hematoxylin and eosin (HE) staining, the effects of FL administration on each adipose tissue were observed, and expression analysis of mitochondrial DNA genes was performed.

Results: Repeated administration of FL had no morphological effects on brown adipose tissue or visceral fat. However, FL significantly reduced the cell size in subcutaneous fat and induced the appearance of multilocular structures. Furthermore, FL increased cytochrome B expression in subcutaneous fat. The results showed that FLs induce browning of subcutaneous fat in mice.

Conclusion: This study showed that FL-induced enhancement of sympathetic nerve activity increased mitochondria in subcutaneous fat and promoted browning. However, no changes were observed in other adipose tissues. Further long-term administration is required to analyze the effects of FLs on adipose tissue thoroughly.

Keywords: brown adipose; epididymal adipose; flavan 3-ols; inguinal adipose; sympathetic nerve.

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Conflict of interest statement

Conflict of interest: Prof. Calabrese is Editor in Chief, and Prof. Osakabe is the Editor of Open Medicine Journal. This fact has not affected the peer review process.

Figures

Figure 1
Figure 1
Histochemical image of brown adipose tissue (BAT) in mice either fed standard (left) or high-fat diet (right) after distilled water (DW) administration or 50 mg/kg flavan (FL) for 2 weeks. The upper panel shows the DW-administered group, while the lower panel illustrates the FL-administered group. Both images have been magnified 400× or 1,000×.
Figure 2
Figure 2
Histochemical image of visceral epididymal adipose (eWAT) in mice either fed standard (left) or high-fat diet (right) after distilled water (DW) administration or 50 mg/kgflavan 3-ols (FL) for 2 weeks. The upper panel shows the DW-administered group, while the lower panel illustrates the FL-administered group. Both images have been magnified 400× or 1,000×.
Figure 3
Figure 3
Histochemical image of subcutaneous inguinal adipose (iWAT) in mice either fed standard (left) or high-fat diet (right) after distilled water (DW) administration or 50 mg/kgflavan 3-ols (FL) for 2 weeks. The upper panel shows the DW-administered group, while the lower panel illustrates the FL-administered group. Both images have been magnified 400× or 1,000×.
Figure 4
Figure 4
Mitochondrial DNA expression in brown (BAT, a), epididymal (eWAT, b), and inguinal adipose (iWAT, c) determined by RT-PCR. Each value represents mean ± standard deviation (n = 8, each). Statistical analyses were performed using non-parametric Wilcoxon and MannWhitney U tests. Cyt B, cytochrome B.

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