Direct oral and fiber-derived butyrate supplementation as an anti-obesity treatment via different targets
Zuzanna Majka, Barbara Zapała, Agnieszka Krawczyk, Krzysztof Czamara, Joanna Mazurkiewicz, Ewa Stanek, Izabela Czyżyńska-Cichoń, Mariusz Kępczyński, Dominika Salamon, Tomasz Gosiewski, Agnieszka Kaczor
Abstract
BACKGROUND & AIMS: Butyric (one of the short-chain fatty acids), a major byproduct of the fermentation of non-digestible carbohydrates (e.g. fiber), is supposed to have anti-obesity and anti-inflammatory properties. However, butyrate's potential and mechanism in preventing obesity and the efficient form of administration remain to be clarified. METHODS: Hence, we studied the effect of oral supplementation with 5% (w/w) sodium butyrate and 4% (w/w) β-glucan (fiber) on young male mice (C57BL/6J) with high-fat diet-induced obesity (HFD: 60 kcal% of fat + 1% of cholesterol). Six weeks old mice were fed diets based on HFD or control (AIN-93G) diet with/without supplements for 4 weeks. The unique, interdisciplinary approach combining several Raman-based techniques (including Raman microscopy and fiber optic Raman spectroscopy) and next-generation sequencing was used to ex vivo analyze various depots of the adipose tissue (white, brown, perivascular) and gut microbiome, respectively. RESULTS: The findings demonstrate that sodium butyrate more effectively prevent the pathological increase in body weight caused by elevated saturated fatty acids influx linked to a HFD in comparison to β-glucan, thereby entirely inhibiting diet-induced obesity. Moreover, butyrate significantly affects the white adipose tissue (WAT) reducing the epididymal WAT mass in comparison to HFD without supplements, and decreasing lipid saturation in the epididymal WAT and perivascular adipose tissue of the thoracic aorta. Contrarily, β-glucan significantly changes the composition and diversity of the gut microbiome, reversing the HFD effect, but shows no effect on the epididymal WAT mass and therefore the weight gain inhibition is not as effective as with sodium butyrate. CONCLUSIONS: Here, oral supplementation with sodium butyrate and β-glucan (fiber) has been proven to have an anti-obesity effect through two different targets. Administration-dependent effects that butyrate imposes on the adipose tissue (oral administration) and microbiome (fiber-derived) make it a promising candidate for the personalized treatment of obesity.