Summary The metabolic improvement effect of blueberries has long been recognized, although its precise mechanism(s) remains obscure. Here, we show that phenolic blueberry extract (BE) treatment improved diet- and genetically induced metabolic syndromes, which were linked to increased energy expenditure in brown adipose tissue (BAT) and improved lipid metabolism in the liver via pathways involving the bile acid (BA) receptors TGR5 and FXR. These observations were strongly correlated with the regulation of BAs (e.g., a decrease in the FXR inhibitors TαMCA and TβMCA) and the gut microbiota (GM) (e.g., an expansion of Bifidobacteria and Lactobacillus ), because antibiotic treatment completely blunted the regulation of the GM and BAs and the metabolic effects of BE. We also observed similar results in db/db mice. Furthermore, treating mouse primary cells derived from the liver and BAT with the combinations of BAs mimicking the in vivo alterations upon BE treatment mirrored the in vivo observations in mice.

Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.

Vanillin, a simple phenolic compound, exists marginally in some plants and can be produced by microbes. This study uses high-fat-diet (HFD) induced obese mice to study the effect of vanillin on obesity and obtain positive results. First, both body and adipose tissue weight are reduced. Second, the blood properties signaling certain disorders such as ALT, LDH, glucose, cholesterol, LDL-C, TG and HDL-C are ameliorated and both insulin sensitivity, and glucose tolerance are improved. Third, vanillin reduced elevated levels of inflammatory factors including LPS, IL-6, and TNF-α in plasma and liver tissue resulting from obesity. Finally, the production of short chain fatty acids (SCFAs) is enhanced. Additionally, study results demonstrate that vanillin significantly alleviates obesity-related gut microbiota (GM) disorders including the decrease of alpha- and beta-diversity. Furthermore, vanillin reduces the abundance of Firmicutes phylum, increases the richness of Bacteroidetes and Verrucomicrobiota phyla, and inhibits the expansion of the lipopolysaccharide (LPS)-producing bacteria Bilophila genus and the H2S-producing bacteria Desulfovibrio genus.

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