Chronic administration of a calafate (Berberis microphylla) polyphenol-rich extract modulates gut microbiota and metabolic homeostasis associated with thermogenic activation in high-fat diet-fed mice.

Obesity is characterized by a pathological increase in white adipose tissue (WAT). In addition to WAT, humans and animals have brown (BAT) and beige adipose tissue, specialized in thermogenesis. Increasing thermogenesis could help treat obesity. Polyphenols, such as those found in Calafate (Berberis microphylla), promote thermogenesis, but their effectiveness depends on gut microbiota (GM) composition. This study aimed to evaluate the impact of a Calafate extract on GM composition and thermogenic activity of brown and beige adipose tissue in mice fed a high-fat diet (HFD). Forty 8-week-old C57BL/6J mice were subdivided into 4 groups: control diet (C), control/Calafate diet (CC), high-fat diet (HF) and high-fat/Calafate diet (HFC). CC and HFC groups received daily 50 mg total polyphenols/kg body weight of Calafate extract in the drink for 4 months. Before euthanasia, mice underwent an energy expenditure (EE) measurement. RT-PCR was used to evaluate transcripts of thermogenic markers in ATs. Short-chain fatty acids (SCFAs) and GM composition were analyzed in cecal contents. Calafate extract administration reduced weight gain and increased EE, regardless of diet. It also enhanced the expression of thermogenic markers in BAT and inguinal WAT. While no significant changes in GM α-diversity were found, Calafate extract administration influenced GM composition. Additionally, correlations were observed between thermogenic markers and the abundance of specific gut bacteria. In conclusion, Calafate extract prevents excessive weight gain in HFD-fed male mice, potentially via a thermogenic transcriptional response associated with an enriched abundance of SCFA-producing bacteria.